5-hydroxytryptamine releases adenosine 5'-triphosphate from nerve varicosities isolated from the myenteric plexus of guinea-pig ileum.

5-Hydroxytryptamine (5-HT)-evoked release of ATP from nerve varicosities isolated from the myenteric plexus of guinea pig ileum was investigated. 5-HT released ATP from myenteric varicosities by a Ca2+-dependent mechanism. The EC50 for release of ATP was 7 X 10(-7) M 5-HT. 5-HT-evoked release of ATP was not blocked by tetrodotoxin (TTX), indicating that release was not initiated by the opening of Na+-channels in the isolated myenteric varicosities. Release of ATP by 5-HT was diminished to 56% of control values by in vivo pretreatment of the guinea-pig with 6-hydroxydopamine (6-OHDA, 250 mg kg-1, i.p.) for 24 h. 6-OHDA pretreatment caused extensive destruction of noradrenergic varicosities as indicated by an 87% loss of noradrenaline content. Quipazine (5 X 10(-6) M) and methysergide (10(-4) M) caused a small release of ATP and blocked subsequent 5-HT-induced release of ATP. Metergoline (2.5 X 10(-5) M), (+)-tubocurarine (7 X 10(-5) M) and cocaine (10(-4) M) decreased 5-HT-induced ATP release. 5-Methoxytryptamine (10(-4) M), picrotoxin (3.5 X 10(-6) M), spiroperidol (10(-6) M), morphine (1.3 X 10(-6) M) and phenoxybenzamine (3.7 X 10(-7) M) were ineffective. The results demonstrate a 5-HT-receptor-mediated release of ATP from noradrenergic and possibly non-adrenergic varicosities in the myenteric plexus of guinea-pig ileum. The 5-HT-induced release of ATP is consistent with a possible transmitter, cotransmitter or modulatory role for ATP in the myenteric plexus.