Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals.
Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine. Preincubation of the excised choroid with pertussis toxin (200 ng/ml) reverses the inhibitory effects of both morphine and somatostatin. In contrast, 3H-ACh release from terminals in the striated iris is not affected by either morphine or somatostatin at micromolar levels. These results suggest that both opiate and somatostatin receptors are present in the choroid target and that they may act through a final common pathway to modulate ACh release via G proteins. Second messengers such as cyclic AMP or diacylglycerol do not appear to mediate these effects; neither increasing cAMP levels in terminals nor activation of protein kinase C affects evoked release or its inhibition by morphine or other neuromodulators. It is unclear whether endogenous neuromodulation occurs in this system, although somatostatin-like immunoreactivity can be demonstrated in terminals of choroid neurons.
Gray
D B
DB
Department of Physiology, University of Connecticut, Storrs 06268.
Pilar
G R
GR
Ford
M J
MJ
D000109:Acetylcholine / Q000096:biosynthesis; D000818:Animals; D001696:Biomechanical Phenomena; D002645:Chickens; D002794:Choline / Q000378:metabolism; D002829:Choroid / Q000294:innervation; D005726:Ganglia, Parasympathetic / Q000378:metabolism; D007498:Iris / Q000294:innervation; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009411:Nerve Endings / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*; D015290:Second Messenger Systems
D009294:Narcotics; D018377:Neurotransmitter Agents; D010455:Peptides; D009020:Morphine; D002794:Choline; D000109:Acetylcholine