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Nonsulfated CC[K.sub.58] [CC[K.sub.58](ns)] has not been considered to be of biological importance because CC[K.sub.58](ns) binds poorly to the CC[K.sub.A] receptor and has only been identified once in intestinal extracts. In this work, a radioimmunoassay specific for the COOH-terminal region of gastrin and CCK (antibody 5135) was used to monitor the purification of CCK molecular forms from canine intestinal extracts. A minor immunoreactive peak was associated with a major absorbance peak during an ion-exchange, HPLC step. Characterization of this minor immunoreactive peak demonstrated that it was CC[K.sub.58](ns). CC[K.sub.58](ns) is 14% as immunoreactive as sulfated CC[K.sub.8] [CC[K.sub.8](s)]. Amino acid analysis demonstrated that CC[K.sub.58](ns) was present at 50% the amount of CC[K.sub.58](s). In addition, we found that CC[K.sub.58](ns) does not potently displace an [sup.125]I-labeled CC[K.sub.10] analog from the CC[K.sub.A] receptor in mouse pancreatic membranes and does not stimulate amylase release from isolated pancreatic acini, or stimulate pancreatic secretion in an anesthetized rat model. By contrast, CC[K.sub.58](ns) does bind to CC[K.sub.B] receptors and stimulates gastric acid secretion via this receptor. The presence of CC[K.sub.58](ns) and its ability to selectively stimulate the CC[K.sub.B] receptor without stimulation of the CC[K.sub.A] receptor suggest that CC[K.sub.58](ns) may have unique physiological properties, especially tissues where the nonsultated peptide can act as a paracrine or neurocrine agent. gallbladder: pancreas; gastric acid; receptor binding; CC[K.sub.A]; CC[K.sub.B]

We hypothesized that neurogenic inflammation is a common final pathway for parenchymal inflammation in pancreatitis and evaluated the role of primary sensory neurons in secretagogue-induced and obstructive pancreatitis. Neonatal rats received either the primary sensory neuron-denervating agent capsaicin (50 mg/kg sc) or vehicle. At 8 wk of age, pancreatitis was produced by six hourly injections of caerulein (50 [micro]g/kg ip) or by common pancreaticobiliary duct ligation (CPBDL). The severity of pancreatitis was assessed by serum amylase, pancreatic myeloperoxidase (MPO) activity, histological grading, pancreatic plasma extravasation, and wet-to-dry weight ratio. Caerulein significantly increased MPO activity and wet-to-dry weight ratio, produced histological evidence of edematous pancreatitis, induced plasma extravasation, and caused hyperamylasemia. CPBDL increased MPO activity and produced histological evidence of pancreatitis. Neonatal capsaicin administration significantly reduced tissue MPO levels, histological severity scores, and wet-to-dry weight ratio and abolished plasma extravasation. These results demonstrate that primary sensory neurons play a significant role in the inflammatory cascade in experimental pancreatitis and appear to constitute a common final pathway for pancreatic parenchymal inflammation. caerulein; capsaicin; common pancreaticobiliary duct ligation; neurogenic inflammation; substance P

There have been no studies in any vertebrate that have localized insulin-like growth factor (IGF)-I receptors in prolactin (PRL) cells or that have correlated pituitary binding to the potency of IGF-I in regulating both PRL and growth hormone (GH) secretion. We show that IGF-I binds with high affinity and specificity to the pituitary gland of hybrid striped bass (Morone saxatilis x M. chrysops). IGF-I and IGF-II were equipotent in inhibiting saturable [sup.125]I-IGF-I binding, whereas insulin was ineffective. IGF-I that binds with similar affinity to the rostral pars distalis (>95% PRL cells) as the whole pituitary gland and immunohistochemistry colocalizes IGF-I receptors and PRL in this same region. Des(1-3)IGF-I, a truncated analog of IGF-I that binds with high affinity to IGF-I receptors but weakly to IGF-I binding proteins (IGFBPs), showed a similar inhibition of saturable [sup.125]I-IGF-I binding, but it was more potent than IGF-I in stimulating PRL and inhibiting GH release. These results are the first to localize IGF-I receptors to PRL cells, correlate IGF-I binding to its efficacy in regulating GH and PRL secretion, as well as demonstrate that IGFBPs may play a significant role in modulating the disparate actions of IGF-I on PRL and GH secretion. signal transduction; teleost; insulin-like growth factor binding proteins; Morone; secretion

A study of the action of calcium in the bombesin-activated secretion of cholecystokinin (CCK) from intestinal CCK-generating cell-line (STC-1) through radioimmunoassay reveals that the secretion occurs through binding to a receptor and is influenced by enhanced (Ca2+)i. STC-1 cell line may facilitate the analysis of the modulation of intestinal CCK release. Bombesin induces a dose-dependent secretion of CCK, which requires calcium intake.

Capsaicin vanilloid receptor-1 mediates substance P release in experimental pancreatitis. Am J Physiol Gastrointest Liver Physiol 281: G1322-G1328, 2001.--We examined whether the capsaicin vanilloid receptor-1 (VR1) mediates substance P (SP) release from primary sensory neurons in experimental pancreatitis. Pancreatitis was achieved by 12 hourly injections of caerulein (50 [micro]g/kg ip) in mice. One group received capsazepine (100 [micro]mol/kg sc), a competitive VR1 antagonist, at 4-h intervals. Neurokinin-1 receptor (NK1R) internalization in acinar cells, used as an index of endogenous SP release, was assessed by immunocytochemical quantification of NK1R endocytosis. The severity of pancreatitis was assessed by measurements of serum amylase, pancreatic myeloperoxidase (MPO) activity, and histological grading. Caerulein administration caused significant elevations in serum amylase and pancreatic MPO activity, produced histological evidence of pancreatitis, and caused a dramatic increase in NK1R endocytosis. Capsazepine treatment significantly reduced the level of NK1R endocytosis, and this was associated with similar reductions in pancreatic MPO activity and histological severity of pancreatitis. These results demonstrate that repeated caerulein stimulation causes experimental pancreatitis that is mediated in part by stimulation of VR1 on primary sensory neurons, resulting in endogenous SP release. capsazepine; neurogenic inflammation; neurokinin-1 receptor; pancreatic acinar cells; primary sensory neurons