Effect of selective serotonin receptor agonists on prolactin secretion in male rats.
The effect of different serotonin (5-HT) receptor agonists on the release of prolactin (PRL) was investigated in conscious male rats. The 5-HT1 receptor agonists 5-carboxamidotryptamine and RU 24969 stimulated the PRL secretion dose dependently. RU 24969 possessed almost the same potency and efficacy (maximal effect) as 5-HT, while 5-carboxamidotryptamine was more potent and had a higher efficacy. The 5-HT1 + 2 receptor agonist MK 212 stimulated the PRL secretion only at high doses. The 5-HT2 receptor agonist S(alpha)methyl-5-HT and the 5-HT3 receptor agonist 2-methyl-5-HT had minor or no effect on the PRL secretion. The PRL-releasing effect of submaximal doses of 5-carboxamidotryptamine and RU 24969 was blocked by the 5-HT1 + 2 receptor antagonist methysergide and enhanced by other 5-HT agonists, but was unaffected by the 5-HT2 and 5-HT3 receptor antagonists. MK 212, S(alpha)methyl-5-HT, and--in particular--2-methyl-5-HT potentiated the effect of 5-carboxamidotryptamine. Likewise, 2-methyl-5-HT potentiated the effect of RU 24969, while MK 212 or S(alpha)methyl-5-HT had an additive to slightly potentiating effect. The findings show that 5-HT stimulates PRL secretion via 5-HT1 as well as 5-HT2 receptors and that activation of 5-HT2 and 5-HT3 receptors significantly augment the PRL-stimulating effect of 5-HT1 receptor activation. This indicates that the 5-HT receptor subtypes may interact functionally in the mediation of the PRL-releasing effect of the serotonergic system.
Jørgensen
H
H
Department of Medical Physiology, Panum Institute, University of Copenhagen, Denmark.
Knigge
U
U
Warberg
J
J
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004357:Drug Synergism; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011388:Prolactin / Q000378:metabolism*; D011719:Pyrazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D007211:Indoles; D011719:Pyrazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D012701:Serotonin; C014896:6-chloro-2-(1-piperazinyl)pyrazine; D011388:Prolactin; C047087:5-carboxamidotryptamine