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‐HT 1A+1B+5A+7 agonist 5‐carboxamidotryptamine (5‐CT), the 5‐HT 2A+2C agonist DOI, the 5‐HT 2C+2A agonist mCPP, the 5‐HT 2C agonist MK‐212, the 5‐HT 3 agonist SR 57277 and the 5‐HT 4 agonist RS 67506. The 5‐HT 1A 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‐HT 1A ), LY 53857 (5‐HT 2A+2C ), ICS 205‐930 (5‐HT 3+4 ) and RS 23597 (5‐HT 4 ). The 5‐HT 2+6+7 antagonist metergoline in combination with the 5‐HT 1A+2+7 antagonist methysergide inhibited the stimulatory effect of 5‐CT on both hormones, whereas the 5‐HT 1A+1B antagonist cyanopindolol only inhibited the oxytocin response. The 5‐HT 2A antagonist 4‐(4‐flourobenzoyl)‐1‐(4‐phenylbutyl)‐piperidine oxalate had no effect on DOI‐induced hormone response. The 5‐HT 2C 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‐HT 2C , 5‐HT 4 and 5‐HT 7 receptors, whereas 5‐HT 2A , 5‐HT 3 and 5‐HT 5A receptors seem to be of minor importance. 5‐HT‐induced oxytocin secretion involves 5‐HT 1A , 5‐HT 2C and 5‐HT 4 receptors; in addition an involvement of 5‐HT 1B , 5‐HT 5A and 5‐HT 7 receptors seems likely, whereas 5‐HT 2A and 5‐HT 3 receptors seem to be less important.