MEMBRANE DELIMITED AND INTRACELLULAR SOLUBLE PATHWAYS IN THE SOMATOSTATIN MODULATION OF ACH RELEASE

The signal transduction cascade between the activation of the somatost atin (SOM) receptor and modulation of transmitter release was study us ing Acetylcholine (ACh) release measurements and patch clamp recording s of Ca2+ current from acutely dissociated St 40 ciliary ganglion neur ons. As in intact synapses, somal ACh release was blocked by 100 nM SO M or 100 mu M dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 mu M I-NAME (a selective inhibitor of nitric oxide syn thase, NOS) or 100 mu M Rp-8p-CPT-cGMPs (a selective inhibitor of a cG MP protein dependent kinase, PKG). In whole cell recordings, SOM inhib ition of Ca2+ current rapidly relaxes to control levels but is sustain ed in perforated patch recordings which decreases cell dialysis. Inhib ition of NOS or PKG in perforated patch recordings, however caused SOM effects to become transient again. We hypothesize that PKG alters the characteristics of the membrane-delimited G protein inhibition of Ca2 + current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converg ing on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current l eading to a decrease in transmitter release.