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In the present study we have identified biochemically DA receptors in rat Lower Esophageal Sphincter (LES) and have identified their role in the control of the sphincter motility. Dopamine (DA) both stimulated and inhibited cyclic AMP formation in rat LES; the pharmacological characterization of these effects indicated that they were mediated by D-1 and D-2 receptors, respectively. The results obtained with LES helical strips showed that DA plays both inhibitory and stimulatory effects on the sphincter function; the pharmacological characterization with selective D-1 and D-2 agonists and antagonists strongly suggested that D-1 receptors are involved in LES contraction, while D-2 receptors mediate the relaxation of the sphincter. The same results were obtained by measuring intraluminal LES pressure in anesthetized rats. The selective D-1 agonist fenoldopam (40 micrograms/kg, i.v.) increased the LES pressure; on the other hand bromocriptine (10 micrograms/kg, i.v.), which preferentially interacts with D-2 receptors, induced a decrease of the resting LES pressure.

Sulpiride is a new neuroleptic which does not produce extrapyramidal side effects in humans nor catalepsy in experimental animals. Sulpiride in rat striatum and nucleus accumbens homogenates fails to block adenylate cyclase activation induced by both dopamine and apomorphine. Moreover the in vivo cyclic adenosine monophosphate accumulation induced by apomorphine in the striatum of rats is not blocked by sulpiride as haloperidol and other classic neuroleptic do. Sulpiride appears to be unique in respect to other neuroleptic since according to the experiments reported in this paper it does not block dopamine receptors either in vitro or in vivo.

A significant decrease in the number of β-adrenergic receptors was observed in cerebral microvessels of fatty (fa/fa) and streptozotocin-induced diabetic rats, without receptor affinity changes. These results suggest that alterations of central adrenergic regulation of small vessels may be involved in brain microvasculature disturbances that occur with diabetes.

Many butyric acid congeners were screened for their behavioural effect and for their influence on brain amines. Among the compounds examined, all butyric acid derivatives endowed with depressant action on the CNS, and only those endowed with such action, were capable of increasing selectively brain DA. Brain NE and serotonin were not influenced. Besides -OH and -BL, the following compounds were found to be active: 1,4-BD, α-OH-butyric acid, -BL- -carboxylic acid and succinate. 1,4-BD was studied in detail in rats and in rabbits. The effect of this compound shows close similiarities to that of -OH. There is a direct correlation between the degree of sedation produced by this compound an the accumulation of DA in the brain. This is particularly evident in rabbits: the anaesthetic effect occurs after a delay of about two hours, as does the rise in brain DA. The DA levels return to normal when the animals are awake. The newly-formed DA is localized in the pallidum and in the striatum. The mechanism by which the above compounds, and specifically 1,4-BD, produce the change in brain DA is not clear: 1,4-BD, like -OH, does not inhibit MAO either in vivo or in vitro. The fact that 1,4-BD produces its effect after a long delay suggests that it acts through an active metabolite.

The efficacy of anorectic drugs has been studied in rats made hyperphagic by injection of insulin or of 2-deoxy-d-glucose (2-DG). It was found that anorectics that act through a serotoninergic mechanism, i.e., d- and d-l-fenfluramine, p-chloroamphetamine, quipazine and fluoxetine antagonize both insulin- and 2-DG-induced overeating, while anorectics acting through the dopaminergic system, i.e., d-amphetamine, diethylpropion, lisuride, bromocriptine and mazindol, antagonize the hyperphagia induced by 2-DG but not that induced by insulin. Neither serotoninergic nor dopaminergic anorectics modified insulin-induced hypoglycaemia. The serotonin (5-HT) receptor blocker metergoline did not modify the hyperphagic response to insulin or 2-DG. The present results indicate that there are different neuronal or humoral circuits underlying the hyperphagic responses to insulin and 2-DG. In addition, these results, which show different effectiveness of anorectic drugs depending on what has provoked the hyperphagia, suggest that differences in the etiology of the hyperphagia of obese subjects must be taken into consideration when choosing therapy.

Bromocriptine injected to rats induces an increase of cAMP levels in the striatum in vivo. The time course of this increase is very similar to that of apomorphine. However bromocriptine does not stimulate striatal dopamine-sensitive adenylate cyclase but surprisingly antagonized the activation of this enzyme elicited by dopamine. Possible hypotheses on various sites of action of the drug are discussed.

Dihydroergotoxine (10 micrograms/kg s.c.) decreased mean carotid blood pressure in urethane-anaesthetized spontaneously hypertensive rats but failed to modify the same parameter in normotensive rats. The effect was statistically significant 20 min after the injection and relatively long lasting (up to 90 min). Pharmacological characterization of the phenomenon indicated that it is mediated by stimulation of dopamine receptors, since pretreatment with haloperidol, cis-flupentixol but not with trans-flupentixol, completely prevent the reduction in blood pressure induced by dihydroergotoxine. Moreover, a challenge dose of dihydroergotoxine did not reduce mean blood pressure values in spontaneously hypertensive rats pretreated with domperidone or (-)sulpiride, but not with (+)sulpiride. These results suggest that the ergot derivative modifies the cardiovascular system by interaction with peripheral dopamine receptors of the DA2 type.

Dopamine receptors in bovine adrenal cortex have been studied by using 3 H-(−)sulpiride as selective ligand. The specific binding is saturable and the Scatchard analysis reveals a single component with a Kd of 6.2 nM and a Bmax of 8 fmoles/mg protein. The characterization indicates that the binding is rapid, reversible, stereospecific, Na + - and temperature- dependent. Moreover its pharmacological profile is superimposable to that of D-2 receptors in the striatum, thus suggesting that central and peripheral D-2receptors are identical.

Chronic ethanol consumption induces an increase in striatal 3H-Spiroperidol and 3H(-)Sulpiride specific binding by enhancing the affinity between the different dopaminergic recognition sites and the labelled ligands. Dopamine (DA) receptor supersensitivity is also suggested by the enhanced effect of neuroleptics in inducing hypomotility in rats treated with ethanol. The results, obtained by means of the administration of neuroleptics in comparison to ethanol treated rats, indicate a lack of cross tolerance between ethanol and other drugs acting on the dopaminergic recognition sites. These data suggest that ethanol effects on the dopaminergic system are mediated by events involving other neurotransmitter systems.

The intragastric of intraperitoneal administration of metergoline (2.5–10 mg/kg) stimulates dopamine (DA) synthesis in the rat and mouse brain. In vitro, metergoline blocks DA-sensitive adenylate cyclase and displaces H 3 -haloperidol from specific binding sites in striatal homogenates.