Serotonin receptors involved in vasopressin and oxytocin secretion

Serotonin (5-HT), 5-HT agonists, the 5-HT precursor 5-hydroxytryptophan, 5-HT-releasers and -reuptake inhibitors stimulate the release of vasopressin and oxytocin. We investigated the involvement of 5-HT receptors in the serotonergic regulation of vasopressin and oxytocin secretion. Vasopressin and oxytocin secretion was stimulated by 5-HT, the 5-HT1A+1B+5A+7 agonist 5-carboxamidotryptamine (5-CT), the 5-HT2A+2C agonist DOI, the 5-HT2C+2A agonist mCPP, the 5-HT2C agonist MK-212, the 5-HT3 agonist SR 57277 and the 5-HT4 agonist RS 67506. The 5-HT1A agonist 8-OH-DPAT, which had no effect on vasopressin secretion, stimulated oxytocin secretion. The 5-HT-induced release of vasopressin and oxytocin was inhibited by central infusion of the 5-HT antagonists WAY 100635 (5-HT1A ), LY 53857 (5-HT2A+2C ), ICS 205-930 (5-HT3+4 ) and RS 23597 (5-HT4 ). The 5-HT2+6+7 antagonist metergoline in combination with the 5-HT1A+2+7 antagonist methysergide inhibited the stimulatory effect of 5-CT on both hormones, whereas the 5-HT1A+1B antagonist cyanopindolol only inhibited the oxytocin response. The 5-HT2A antagonist 4-(4-flourobenzoyl)-1-(4-phenylbutyl)-piperidine oxalate had no effect on DOI-induced hormone response. The 5-HT2C antagonist Y 25130 partly inhibited the stimulating effect of MK-212. ICS 205-930 and RS 23597 inhibited vasopressin and oxytocin secretion induced by RS 67506. WAY 100635 inhibited 8-OH-DPAT-induced oxytocin secretion. We conclude that 5-HT-induced vasopressin secretion primarily is mediated via 5-HT2C , 5-HT4 and 5-HT7 receptors, whereas 5-HT2A , 5-HT3 and 5-HT5A receptors seem to be of minor importance. 5-HT-induced oxytocin secretion involves 5-HT1A , 5-HT2C and 5-HT4 receptors; in addition an involvement of 5-HT1B , 5-HT5A and 5-HT7 receptors seems likely, whereas 5-HT2A and 5-HT3 receptors seem to be less important.