Membrane delimited and intracellular soluble pathways in the somatostatin modulation of ACh release.
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 Ca2+ current from acutely dissociated St 40 ciliary ganglion neurons. As in intact synapses, somal ACh release was blocked by 100 nM SOM or 100 microM dibutyril cGMP, and the SOM-mediated inhibition could be reversed by 10 microM 1-NAME (a selective inhibitor of nitric oxide synthase, NOS) or 100 microM Rp-8p-CPT-cGMPs (a selective inhibitor of a cGMP protein dependent kinase, PKG). In whole cell recordings, SOM inhibition of Ca2+ 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 Ca2+ current. Therefore SOM receptors trigger a membrane-delimited signal transduction cascade that is modulated by soluble messengers, converging on voltage activated Ca2+ channels. When both pathways are active together, SOM causes a sustained inhibition of neuronal Ca2+ current leading to a decrease in transmitter release.
Pilar
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Department of Physiology and Neurobiology, Univ. of Connecticut, Storrs 06269-4156, USA.
Gray
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Meriney
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D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002645:Chickens; D002829:Choroid / Q000378:metabolism; D002924:Ciliary Body / Q000294:innervation / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D015290:Second Messenger Systems; D015398:Signal Transduction; D013004:Somatostatin / Q000378:metabolism*
D013004:Somatostatin; D006152:Cyclic GMP; D000109:Acetylcholine; D002118:Calcium