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In this study, we evaluated the mechanism of action whereby cholecystokinin increases spike-burst rate of the opossum sphincter of Oddi (SO). Each spike burst corresponds to a peristaltic SO contraction. Two types of animal preparations were evaluated: (1) awake chronic animal preparations and (2) anesthetized animals. A total of 19 chronic animals were prepared by implantation of electrodes on the SO, gastric antrum, duodenum, and jejunum. SO spike-burst rate was stimulated by intravenous infusion of CCK-OP (10 ng/kg/min), feeding, or intraduodenal infusion of fat-containing nutrient. Each stimulus was begun 20 min after cessation of phase III duodenal MMC activity and caused an increase in SO spike-burst rate from about 2 to 6/min that lasted for less than or equal to 1 hr. Such increases were antagonized substantially by hexamethonium, atropine, or methysergide. The CCK antagonist, L364718, antagonized the excitatory SO response to CCK-OP infusion or intraduodenal infusion of fat-containing nutrient (Isocal) but did not antagonize the response to feeding; CR1409 had no antagonistic effect on SO response to any of the three types of stimuli. In the acute studies in anesthetized animals, an intravenous bolus dose of CCK-OP (800 ng/kg) caused a substantial increase in SO spike-burst rate that was antagonized by CR1409 but not by atropine, hexamethonium, methysergide, L364718, or TTX.(ABSTRACT TRUNCATED AT 250 WORDS)

In this study, we evaluated the effect of histamine on phasic contractile activity in the opossum sphincter of Oddi (SO). SO manometry was done in 35 animals, using an infused catheter system with minimal compliance. In anesthetized animals, phasic SO contractions occurred at a frequency of 7.3 +/- 0.3 (SE) contractions/min with an amplitude of 83 +/- 4 mmHg. Intravenous histamine (5-80 micrograms/kg) invariably inhibited the frequency and amplitude of SO phasic contractions. At larger doses, the SO contractions were abolished for several minutes. The SO inhibitory effect of histamine was duplicated by the selective H1-agonist, 2-pyridylethylamine, and abolished by H1-blockade with pyrilamine or neural blockade with tetrodotoxin. After tetrodotoxin, histamine and 2-pyridylethylamine caused an increased frequency and amplitude of SO contractions. This excitatory effect was blocked by pyrilamine. The histamine effects on SO phasic contractions were not altered by metiamide, atropine, phentolamine, propranolol, hexamethonium, or a large dose of nicotine. We conclude that 1) histamine depresses phasic SO contractions in the opossum; 2) histamine's depressant SO effect is mediated by H1 stimulation of noncholinergic, nonadrenergic SO inhibitory nerves, overriding an H1 stimulatory effect on SO smooth muscle; and 3) histamine has no H2-mediated effect on the opossum SO.

The oppossum sphincter of Oddi (SO) exhibits peristaltic spike bursts with accompanying contraction waves that originate proximally in the sphincter of Oddi and propagate toward the duodenum. In this study we recorded myoelectrical activity of the opossum SO and upper gastrointestinal tract in six conscious animals using chronically implanted electrodes. Biopolar electrodes were implanted in the gastric antrum, duodenum, SO segment, jejunum, and ileum. During fasting the frequency of SO spike bursts, scored as number per minute, showed a cyclic pattern consisting of four phases (A to D). Phase A had a low spike burst frequency of approximately 2/min that lasted approximately 20 min. In phase B, the spike burst frequency increased progressively during a 40-45 min interval culminating in a short interval of phase C activity characterized by a maximal spike burst frequency of approximately 5/min. During phase D, the spike bursts decreased over 15 min to merge with the low frequency of phase A and the cycle repeated. Cycle length of the interdigestive SO cycle, 87+/-11 SD min, was virtually identical with that of the interdigestive migrating myoelectric complex (MMC) of the upper gastrointestinal tract. The onset of phase C activity in the SO began 1-2 min before phase III of the MMC activity in the duodenum. Feeding abolished the cyclic pattern of spike burst activity in the SO as well as in the upper gastrointestinal tract. After feeding the SO spike bursts occurred at a frequency of 5-6/min for at least 3 h. We conclude that: (a) During fasting, the oppossum SO exhibits cyclic changes in its spike burst frequency; (b) Maximal spike burst frequency of the SO occurs virtually concurrent with passage of phase III MMC activity through the duodenum and; (c) Feeding abolishes the interdigestive cyclic spike burst pattern of the SO as well as that of the gastrointestinal tract.

Endoscopic sphincterotomy (ES) alters the structure and motor function of the sphincter of Oddi (SO). The magnitude and duration of these changes, however, have not been critically examined. Before ES, 22 patients with common bile duct stones were evaluated by endoscopic retrograde cholangiography. The pressure gradient between the common bile duct and the duodenum, the SO basal pressure, and the SO peak phasic pressures were obtained. After ES, the electrosurgical incision length was determined using the extended papillotome and an inflated Fogarty balloon as reference. A high correlation existed between the endoscopist's estimate of ES incision size using this technique and the actual length of simulated incisions fashioned in cardboard mounts. These studies were repeated in all 22 patients at 1-yr follow-up and in 8 of these patients at 2-yr follow-up. At 12 mo and 24 mo after ES, the common bile duct (CBD) to duodenal pressure gradient and the sphincter of Oddi basal pressure were virtually eliminated. The amplitude of SO phasic contractions was significantly diminished 12 mo after ES (124 +/- 16 mmHg to 37 +/- 10 mmHg; p less than 0.001), but 24 mo after ES, SO phasic contraction amplitude was not significantly different from the values before ES. Incision length at 1-yr follow-up was reduced in the group of 22 patients from 11.6 +/- 0.8 mm to 8.3 +/- 0.5 mm (p less than 0.001), and in the group of 8 patients from 11.0 +/- 1.5 mm to 7.5 +/- 0.7 mm (p less than 0.025). After an additional 12 mo, however, i.e., 24 mo after ES, the incision length was 6.5 +/- 0.7 mm. There was no significant difference in incision length between the 12-mo and 24-mo examinations. We conclude that after ES, incision length decreases during the first year. There appears to be no further significant reduction in incision length at 2 yr. In addition, the reduction of the CBD to duodenal pressure gradient and the SO basal pressure remain unchanged for at least 2 yr. These manometric findings support the observation that after ES the enlarged opening of the CBD into the duodenum remains open for at least 2 yr.

We evaluated the control mechanism of peristaltic contractions in the opossum sphincter of Oddi (SO) by means of an in vitro preparation. At each of four sites spaced uniformly along the sphincter segment, a force transducer recorded contractions while a monopolar electrode recorded myoelectric activity. Spontaneous myoelectric and contractile activity occurred in 15 of the 20 intact SO specimens studied. Electrical recordings showed characteristic control waves and response activity. Each control wave was invariably accompanied by a phasic contraction, irrespective of whether or not response activity was superimposed on the control wave. The predominant motor activity of the SO was antegrade peristalsis. Retrograde peristalsis occurred when antegrade peristalsis failed to traverse the entire sphincter. Spontaneous SO phasic contractions were not antagonized by tetrodotoxin. Muscle rings sectioned from the SO exhibited spontaneous phasic contractions with a proximal-to-distal gradient of intrinsic contraction frequencies. We conclude that a) the frequency of SO phasic contractions is determined by control wave frequency, b) spontaneous SO peristalsis is myogenic in origin and may be modeled by a linear array of bidirectionally coupled relaxation oscillators, c) the predominance of antegrade peristalsis may be explained by a high-frequency oscillator in the proximal SO that drives the slower, more distal oscillators, d) retrograde peristalsis is initiated by an ectopic oscillator in the distal SO when antegrade contractions fail to propagate the entire length of the SO, and e) ectopic SO contractions can propagate retrograde when the more proximal oscillators are not in their absolutely refractory state.

Papillary stenosis is an imprecisely defined clinical syndrome which eludes definitive diagnosis. In this study we evaluated 26 patients with suspected papillary stenosis by manometric examination of the sphincter of Oddi done during ERCP examination. Basal pressure in the sphincter of Oddi was elevated in 14 of the patients. Of these 14 patients, 10 underwent sphincterotomy and all experienced improvement in clinical symptoms after their surgery. We suggest that ERCP manometry is a useful procedure for identifying patients with papillary stenosis who may benefit from sphincterotomy.

The human sphincter of Oddi (SO) exhibits phasic wave activity over a 4 to 6 mm segment. Approximately 60% of these waves occur in an antegrade direction, 14% are retrograde, and 26% occur simultaneously. Because cholecystokinin-octapeptide (CCK-OP) stimulates the flow of bile into the duodenum, its effect on SO phasic wave contractions and contraction sequences was evaluated at ERCP manometry. An infused triple-lumen catheter of 1.7 mm outer diameter with side orifices spaced 2 mm apart was stationed in the SO segment so that all three orifices recorded phasic pressure waves. We studied 31 patients with normal ductal anatomy and normal SO pressures. In 21 of these patients CCK-OP (20 ng/kg) was given intravenously after a 2- to 3-minute baseline recording was obtained. Pressure recordings were continued for up to 10 minutes following CCK-OP administration. CCK-OP caused a significant inhibition in the frequency and amplitude of SO phasic waves as well as a significant decrease in basal SO pressure. Before CCK-OP most phasic contractions were antegrade, and after CCK-OP the sequence pattern remained unchanged. We conclude that CCK-OP reduces or transiently abolishes SO phasic contractions but that it does not change their temporal sequence. In addition, CCK-OP produces a decrease in basal SO pressure. These findings suggest that the action of CCK-OP in humans is to inhibit SO phasic activity and reduce SO basal pressure to allow increased flow of bile.

We studied the opossum sphincter of Oddi (SO) because in this species the SO is approximately 3 cm in length and its extraduodenal location permits recording of motor activity with negligible interference from duodenal motor activity. The SO segment of 120 animals was evaluated by one or more of the following: (a) intraluminal manometry; (b) electromyography; (c) common bile duct (CBD) flow monitored by a drop counter; (d) cineradiography of intraductal contrast medium; and (e) histologic examination. SO pull-throughs using an infused catheter of 0.6-mm o.d. invariably showed a high pressure zone (HPZ) of 18 +/- 3 SE mm Hg in the terminal 4-5 mm of the SO segment. This HPZ had a narrow lumen, 0.5-0.7 mm in diam, and prominent circular muscle. The HPZ in the terminal SO had both active and passive components. HPZ with minimal amplitude and a paucity of underlying smooth muscle were present inconstantly at the junction of the SO segment with the CBD and pancreatic duct, respectively. The dominant feature of the SO segment was rhythmic peristaltic contractions that originated in the proximal SO and propagated toward the duodenum. These contractions occurred spontaneously at a rate of 2-8/min, ranged up to 200 mm Hg in magnitude, had a duration of approximately 5 s and were not abolished by tetrodotoxin. Concurrent myoelectric and manometric recordings showed that each phasic contraction was immediately preceded by an electrical spike burst. Simultaneous recordings of cineradiography, CBD inflow of contrast medium, SO manometry, and SO electromyography indicated that rhythmic peristaltic contractions stripped contrast medium from the SO into the duodenum. During SO systole, CBD emptying was transiently interrupted, whereas SO filling occurred during the diastolic interval between SO peristaltic contractions. SO distention increased the frequency of SO peristalsis. We conclude that (a) the dominant feature of the opossum SO is rhythmic peristaltic contractions that originate in the proximal SO and propagate toward the duodenum; (b) these forceful SO peristaltic contractions are myogenic in origin and serve as a peristaltic pump that actively empties the SO segment; (c) CBD outflow occurs passively during SO diastole, but is interrupted transiently during each SO peristaltic contraction; and (d) a short HPZ with active as well as passive components exists in the distal SO segment and acts as a variable resistor to SO outflow.

Endoscopic papillotomy was performed in 13 patients after cholecystectomy for retained or recurrent common bile duct calculi (11 patients) and a clinical picture suggesting papillary stenosis (two patients). Following endoscopic papillotomy, ten of the 11 patients spontaneously passed common bile duct (CBD) stones verified on repeated endoscopic retrograde cholangiopancreatography (ERCP) study. One patient failed to pass a large CBD calculus; one patient experienced cholangitis three months after in inadequate papillotomy and required operative intervention. Endoscopic papillotomy substantially decreased the pressure gradient existing between the CBD and the duodenum in all five patients studied with ERCP manometry. Endoscopic papillotomy is a relatively safe and effective procedure for postcholecystectomy patients with retained or recurrent CBD stones. The majority of CBD stones will pass spontaneously if the papillotomy is adequate.

In this study we recorded intraluminal pressure from the human sphincter of Oddi during ERCP examination and determined the effect of enteric hormones on sphincter of Oddi motor function. Studies were obtained in 26 patients who had no demonstrable evidence of pancreaticobiliary disease. After cannulation of the common bile duct (CBD) or pancreatic duct (PD), pressure measurements were made across the sphincter of Oddi (SO) during 1-2 mm incremental withdrawals of the catheter pausing 1 min or longer at each station. The findings showed an SO segment, 4-6 mm in length, that had basal, steady-state pressure about 4 mm Hg higher than CBD or PD pressure. Pronounced phasic contractions were superimposed on the basal SO pressure. These phasic contractions measured 101 +/- 50 SE mm Hg in amplitude and 4.3 +/- 1.5 sec in duration. They had a frequency of 4.1 +/- 0.9/min. Corresponding phasic contractions were not observed in the CBD, PD, or duodenum. Intravenous pulse doses of cholecystokinin octapeptide and glucagon depressed SO motor activity, whereas pentagastrin increased SO pressure. Secretin caused a mixed response of excitation followed by inhibition. We conclude that the human sphincter of Oddi demonstrates unique phasic contractions that are altered by enteric hormones given intravenously. These phasic SO contractions may have an important role in regulating biliary and pancreatic duct employing.

We report a 45-year-old nonalcoholic patient with Von Recklinghausen's disease and chronic recurrent pancreatitis. On endoscopy, a benign-appearing submucosal tumor surrounded the papilla of Vater. Cannulation of the pancreatic duct showed a dilated ductal system with subsequent delayed drainage. Endoscopic manometry revealed elevated sphincter of Oddi pressures. Endoscopic sphincterotomy resulted in immediate normal drainage of the pancreatic duct and in subsequent clinical improvement.

The hospital records of 24 patients with periampullary neoplasms were reviewed. The clinical triad of jaundice, pain, and weight loss and the radiographic imaging triad of dilated biliary ducts, dilated pancreatic duct, and periampullary mass should suggest the diagnosis of periampullary neoplasm.

Forty-seven patients thought to have dysfunction of the sphincter of Oddi were randomly assigned to undergo endoscopic sphincterotomy or sham sphincterotomy in a prospective double-blind study. All the patients had pain resembling biliary pain, had previously undergone a cholecystectomy, and had clinical characteristics suggesting biliary obstruction. The patients were randomly assigned to the treatment (n = 23) or nontreatment (n = 24) group before manometric examination of the sphincter of Oddi was performed. Sphincterotomy resulted in improvement in pain scores at one-year follow-up in 10 of 11 patients with elevated sphincter pressure. In contrast, there was improvement in only 3 of 12 patients with elevated basal sphincter pressures who underwent the sham procedure. In patients with normal sphincter pressure, pain scores were similar regardless of treatment. After one year, sphincterotomy was performed in 12 symptomatic patients who had undergone the sham procedure--7 with elevated sphincter pressures and 5 with normal sphincter pressures. Forty patients were followed for four years. Of the 23 patients with increased sphincter pressure, 10 of the original 11 who underwent sphincterotomy remained virtually free of pain; 7 others who subsequently underwent sphincterotomy also benefited from it. Thus, 17 of 18 patients with sphincter-of-Oddi dysfunction verified by manometry benefited from sphincterotomy. In patients with normal sphincter pressure, sphincterotomy was no more beneficial than sham therapy. Our observations suggest that endoscopic sphincterotomy offers long-term relief of pain in a group of patients with verified sphincter-of-Oddi dysfunction.

In this study, we evaluated the effect of transsphincteric fluid flow on the rate of spike bursts in the opossum sphincter of Oddi (SO). For chronic studies in awake animals, bipolar electrodes were implanted on the SO, gastric antrum, duodenum, and jejunum. In group 1 animals, surgery was limited to electrode implantation. Subsequently, these animals underwent a cholecystectomy. Group 2 animals had electrode implantation without further surgery. In group 3 animals, bile flow was diverted around the SO, whereas in group 4 animals, pancreatic juice as well as bile was diverted around the SO. Multiple myoelectric recordings were obtained in each animal during fasting and after feeding. In fasted control animals, the rate of SO spike bursts showed cyclic increases synchronous with phase III of the duodenal migratory myoelectric complex. Feeding increased the rate of SO spike bursts. Cholecystectomy had no effect on SO spike bursts in fasted animals. Diversion of bile or bile and pancreatic juice around the SO did not alter the fasting pattern of SO spike bursts. However, flow diversion in the group 3 and group 4 animals did cause a modest decrease of SO spike bursts, from approximately 2/min to about 1/min, during phase I of the duodenal migrating myoelectric complex (p less than 0.05). Sphincter of Oddi spike-burst rate was not affected during the remainder of the migrating myoelectric complex cycle. Neither cholecystectomy nor flow diversion caused any change in the normal SO responses to feeding. Excitatory SO responses caused by motilin or by cholecystokinin-octapeptide were shown to be independent of changes in transsphincteric flow. We conclude that variations in transsphincteric flow cause only minimal alteration of the rate of spike bursts in the opossum SO during fasting. Therefore, factors other than transsphincteric flow, such as hormonal or neural influences, appear to be the major mechanism(s) that regulate the rate of SO contractions in awake opossums.

The morphine-Prostigmin test (MPT) has been advocated as a diagnostic test for identifying patients with papillary stenosis. We studied 14 patients referred for possible papillary stenosis with the MPT and ERCP sphincter of Oddi manometry. The response to the MPT (symptoms, serum amylase/lipase values) was evaluated by multiple criteria. The MPT was also done on 6 volunteer control subjects. Operative evaluation of the sphincter of Oddi was obtained in 8 of the 14 patients. There was no correlation between the results of the MPT and ERCP manometry or operative findings. There was good correlation, however, between ERCP manometric findings and operative assessment of the sphincter of Oddi. Fifty percent of the volunteer subjects had a significantly positive enzyme response to the MPT. In our experience the MPT does not reliably detect patients with papillary stenosis.

Our aim in this study is to determine whether extrinsic autonomic nerves regulated spike-burst rate in the opossum sphincter of Oddi (SO) during fasting or after feeding. We implanted electrodes on the distal SO, proximal SO, gastric antrum, duodenum, and jejunum of 20 animals. A cut transection and reanastomosis was done at different levels of the SO to interrupt putative extrinsic or intrinsic nerves, or the SO was painted with phenol to impair extrinsic nerves. Like controls, animals with a cut and reanastomosis at the proximal SO or at the SO-duodenal junction showed a normal fasting pattern of cyclic changes in SO spike-burst rate. In contrast, animals treated by a distal SO cut or phenol treatment at the distal SO lost the normal cyclic pattern of SO spike bursts and had a constant rate of approximately 4/min. A cut through the middle SO uncoupled the spike bursts in the proximal and distal SO. After feeding, all animals developed an SO spike-burst rate of 5-6/min that lasted for several hours. We conclude that the normal fasting pattern of SO spike bursts is regulated by extrinsic nerves that ascend cephalad along the sphincter segment, whereas the sustained increase in SO spike-burst rate after feeding is at least in part hormonal.

In this study we evaluated the effect of enteric hormones on sphincter of Oddi and gastrointestinal spike burst frequency in fasted conscious opossums. A chronic model for obtaining multiple long-term recording of sphincter of Oddi and gastrointestinal myoelectric activity was prepared in 12 animals by implanting bipolar electrodes in the gastric antrum, duodenum, sphincter of Oddi, jejunum, and ileum. Subsequently, 8-18 recording session, 6-8 h in length, were obtained in each animal. Each study was preceded by a 15-h fast. After recording two cycles of the interdigestive migratory myoelectric complex, a 60-min infusion of saline, cholecystokinin-octapeptide, pentagastrin, glucagon, or secretin was begun early in the quiescent period of duodenal activity, 10 min after termination of phase 3 of the migratory myoelectric complex activity. Cholecystokinin-octapeptide (10-80 ng/kg . min) and pentagastrin (25-200 ng/kg . min) increased sphincter of Oddi spike burst frequency while converting interdigestive gastrointestinal myoelectric activity to a fed-like pattern of continuous, irregular spike bursts. Glucagon at high doses of 500 and 1000 ng/kg . min depressed sphincter of Oddi and gastrointestinal spike burst activity, whereas lower doses of glucagon and secretin (3-12 CU/kg . h) had no effect. We conclude that in the opossum, relatively low doses of cholecystokinin-octapeptide and pentagastrin stimulate sphincter of Oddi and gastrointestinal spike burst activity while disrupting the cyclic pattern of sphincter of Oddi and gastrointestinal spike burst activity present during fasting. The physiological significance of these findings remains to be determined.

We evaluated the intramural neural control of the opossum sphincter of Oddi (SO) in an in vitro preparation. Force transducers were used to record contractions at four sites along the sphincter segment. To stimulate intramural nerves, 10- to 120-s trains of pulses (4-10 V amplitude, 0.5 ms duration, and 5 Hz frequency) were delivered to one of three electrode pairs implanted along the SO. Electrical stimulation in the proximal, mid, or distal SO elicited phasic contractions that invariably originated in the proximal SO and propagated antegrade along the entire length of the sphincter segment. Stimulus-evoked contractions resembled spontaneous antegrade peristaltic contractions, but occurred at a higher rate (12-20/min). Atropine completely blocked this excitatory response to nerve stimulation. After atropine, nerve stimulation in the proximal, mid, or distal SO abolished spontaneous contractions at and distal to the site of stimulation for the duration of the stimulus. The inhibitory response to nerve stimulation was completely blocked by tetrodotoxin but was unaffected by phenoxybenzamine, tolazoline, or propranolol. We conclude that 1) the opossum SO is innervated by intramural cholinergic excitatory nerves and nonadrenergic noncholinergic inhibitory nerves; 2) cholinergic excitatory nerves are organized in ascending neural pathways, whereas nonadrenergic noncholinergic inhibitory nerves descend along the length of the SO; and 3) these neural pathways may modulate SO peristalsis in vivo and participate in ascending excitatory and descending inhibitory reflexes.

We studied the effect of motilin on myoelectric activity of the sphincter of Oddi (SO) and upper gastrointestinal tract in conscious opposums. In 17 animals, bipolar electrodes were implanted on the gastric antrum, SO, duodenum, and jejunum. Subsequent 8-h recordings reconfirmed our previous findings that SO spike burst rate changed with interdigestive cycles of the gastrointestinal migrating myoelectric complex (MMC), becoming maximal during passage of phase III activity through the duodenum. In eight animals, peak motilin levels were shown to occur concurrently with maximal SO spike burst rate and MMC phase III activity in the duodenum. Motilin infusion (0.3 and 0.9 micrograms X kg-1 X h-1), given for 30-60 min starting 10 min after duodenal phase III, elicited premature MMC activity that originated in the stomach. Maximal SO activity occurred coincident with passage of premature phase III activity through the duodenum. Pulse intravenous doses of motilin (25-1,600 ng/kg) generally caused an immediate increase in spike burst activity in the gastric antrum, duodenum, and SO that lasted 3-5 min and was often followed by a premature MMC, usually starting in the antrum and progressing through the duodenum and jejunum. Increases in SO spike burst rate also occurred concurrent with motilin-induced, premature duodenal phase III. Motilin given at 5-60% of the duodenal MMC cycle length elicited premature MMCs at 10-60% of the cycle, but no premature MMCs were elicited by any of the motilin doses at the 5% intervals.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of morphine on intraluminal pressures recorded from the sphincter of Oddi (SO) at endoscopic retrograde cholangiopancreatography in 19 patients who were without evidence of biliary or pancreatic disease were studied. Morphine was given in four successive doses of 2.5, 2.5, 5, and 10 micrograms/kg iv at five minute intervals. Morphine in subanalgesic doses increased the frequency of SO phasic pressure waves to a maximum of 10-12/min, caused the phasic waves to occur simultaneously along the sphincter segment, increased phasic wave amplitude from 72 (26) (SE) to 136 (31) mmHg, and increased SO basal pressure from 10 (1) to 29 (9) mmHg (p less than 0.05). The effects of morphine on the SO are mediated by more than one opioid receptor type, as naloxone competitively antagonised the increase in phasic wave frequency induced by morphine, but did not affect the increase in SO basal pressure elicited by morphine. When given after naloxone, morphine decreased phasic wave amplitude, an inhibitory effect that is normally masked by morphine's dominant naloxone sensitive excitatory effect. Mu receptors do not appear to be involved in control of spontaneous SO motor function, as naloxone alone did not affect SO motor activity. The excitatory effects of morphine on the SO are not mediated by cholinergic nerves, as they were not blocked by atropine. Cholinergic nerves, however, may have a role in regulating spontaneous SO motor function because atropine alone depressed phasic wave activity and basal pressure. Although morphine does cause 'spasm' of the human SO, its effects are more complex than is commonly believed.