ABSTRACT
The action of 5-hydroxytryptamine (5-HT) in the rat ileum was analysed pharmacologically. In the isolated rat ileum, either mono or biphasic contraction was induced depending on the concentrations of 5-HT. The former was induced by lower concentrations of 5-HT (less than 6.25 X 10(-7)M) and the latter by higher concentrations of 5-HT (greater than 2.5 X 10 (-6)M). The monophasic contraction and the tonic contraction in response to 5-HT were blocked by methysergide (MTG). The phasic contraction in response to 5-HT after inhibition of muscular receptor with MTG was potentiated by physostigmine and blocked by mecamylamine (MC) or tetrodo-toxin (TTX). The response to 5-HT changed from a contraction to a relaxation by preincubation with MTG plus hyoscine. The relaxation was inhibited by TTX but not by MC and such was provoked even in the ileum from rats treated with 6-hydroxydopamine. Therefore, the inhibitory neuronal receptor for 5-HT does not appear to belong to the adrenergic nervous system. At lower concentrations of 5-HT, relaxation was induced with MTG which was only partially inhibited by TTX. These results indicate that the stimulatory response to 5-HT were caused by activations of muscular receptors and of intramural parasympathetic ganglion cells while inhibitory responses were caused by activations of non-adrenergic inhibitory nerve terminals and of non-neuronal elements.
Subject(s)
Muscle Contraction/drug effects , Muscle Relaxation/drug effects , Muscle, Smooth/drug effects , Serotonin/pharmacology , Animals , Dose-Response Relationship, Drug , Drug Synergism , Hydroxydopamines/pharmacology , Ileum/drug effects , In Vitro Techniques , Male , Mecamylamine/pharmacology , Methysergide/antagonists & inhibitors , Methysergide/pharmacology , Morphine/pharmacology , Physostigmine/pharmacology , Rats , Receptors, Drug , Serotonin Antagonists , Tetrodotoxin/pharmacologyABSTRACT
The acute administration of 2 mg of methysergide significantly reduced plasma prolactin levels in nine normal subjects and in seven hyperprolactinaemic patients. The prolactin lowering effect of this drug was abolished by sulpiride. Morever methysergide lowered plasma GH levels in four out of nine acromegalic patients, who were also responsive to a dopaminergic drug such as bromocriptine. Although methysergide did not significantly blunt the TRH-induced prolactin release, our data suggest that this drug may affect GH and prolactin release through a dopaminergic mechanism of action. This effect should be taken into account when methysergide is employed as antiserotoninergic drug in neuroendocrinological studies.
Subject(s)
Growth Hormone/blood , Methysergide , Prolactin/blood , Receptors, Dopamine/drug effects , Acromegaly/drug therapy , Adult , Female , Humans , Male , Methysergide/antagonists & inhibitors , Methysergide/therapeutic use , Middle Aged , Sulpiride/pharmacologyABSTRACT
1. In subconstrictor doses, both serotonin and methysergide potentiated the vasoconstrictor responses to histamine in the isolated artery of the rabbit ear. 2. In the presence of phentolamine (5 microgram/ml) the potentiating actions of serotonin and methysergide were significantly reduced. 3. This blocking action of phentolamine could be overcome by increasing the concentration of serotonin or by washing the preparation. 4. In arteries taken from rabbits pretreated with reserpine, serotonin still potentiated the response to histamine and phentolamine still blocked this potentiation. 5. The concentration of phentolamine required to block potentiation also blocked the direct constrictor response to serotonin. It did, however, produce a significantly greater blockade of the vasoconstrictor response to noradrenaline. 6. The results indicate that the action of phentolamine in blocking the vascular potentiation produced by serotonin and methysergide is not due to a blockade of alpha-receptors.
