Membrane delimited and intracellular soluble pathways in the somatostatin modulation of ACH release

Abstract

The signal transduction cascade between the activation of the somatostatin (SOM) receptor and modulation of transmitter release was study using Acetylcholine (ACh) release measurements and patch clamp recordings of Ca 2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 μM dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 μM 1-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 μM Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca 2+ current rapidly relaxes to control levels but is sustained in perforated patch recordings which decreases cell dialysis. Inhibition 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 Ca 2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca 2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca 2+ current leading to a decrease in transmitter release.