Adrenergic and possible nonadrenergic sources of adenosine 5'-triphosphate release from nerve varicosities isolated...

Pretreatment of guinea pigs with 6-hydroxydopamine in vivo for 24 h (250 mg/kg i.p.) reduced the norepinephrine and tyrosine hydroxylase contents of varicosities isolated from ileal myenteric plexus by 91 and 89%, respectively, indicating extensive destruction of noradrenergic varicosities. Destruction appeared to be restricted to noradrenergic varicosities because 5-hydroxytryptamine contents were unaffected. In vivo 6-hydroxydopamine treatment reduced the K+- and veratridine-evoked release of ATP from myenteric varicosities by 56 and 63%, respectively, indicating that much, but not all, of the evoked release of ATP probably originated from noradrenergic varicosities. Pretreatment of guinea pigs with 5 mg/kg of reserpine i.p. depleted norepinephrine contents of isolated varicosities by 90% but did not significantly reduce K+- or veratridine-evoked release of ATP, suggesting that the exocytotic release process was unaffected by reserpine. Selective destruction of serotonergic varicosities by treatment of guinea pigs with 50 mg/kg of desmethylimipramine i.p. followed by 40 mg/kg of 5,7-dihydroxytryptamine s.c. failed to diminish K+- or veratridine-evoked release of ATP from myenteric varicosities, indicating that the nonadrenergic release of ATP did not arise from serotonergic varicosities.