Endogenous modulation of ACh release by somatostatin and the differential roles of Ca2+ channels.

The classical neurotransmitter acetylcholine (ACh) and the potential modulatory peptide somatostatin are colocalized in terminals of avian choroid neurons. We previously showed that exogenous somatostatin inhibits ACh release in the choroid coat (Gray et al., 1989b). In the present work we determine whether endogenous somatostatin plays a role in neuromodulation and what mechanisms are involved. To determine its role and its mode of secretion, voltage-sensitive Ca2+ channels in these terminals were identified pharmacologically using Ca2(+)-dependent K(+)-evoked ACh release. Release of the primary transmitter ACh was triggered in the presence of high K+ by Ca2+ influx primarily via dihydropyridine (DHP)-insensitive channels, while inhibition of ACh release occurred when L-type channels were activated by the DHP agonist Bay K 8644. The somatostatin antagonist cyclo(7-aminoheptanoyl-phe-D-trp-lys-thr (BZL)) (CyCam) blocks the inhibition of ACh release induced by the agonist Bay K 8644 and indicates that endogenous somatostatin may normally modulate ACh release. Additionally, nifedipine, a DHP antagonist, and pertussis toxin, known to antagonize somatostatin's effect on ACh release, both reverse the Bay K 8644 effect on ACh release. Although the release of labeled ACh in the first 3 min collection period was not significantly affected by CyCam or nifedipine alone, release in the first minute was enhanced by 50% in the presence of 10 microM nifedipine. Preincubation with CyCam alone also increased ACh release. These results support the hypothesis that endogenous somatostatin is physiologically released during the initial minute of depolarization in high K+ and that this release is mediated by DHP-sensitive Ca2+ channels.