Characterization of the stimulus-induced release of immunoreactive substance P from the myenteric plexus of the guinea-pig small intestine.
The release of immunoreactive substance P (I-SP) from the myenteric plexus of the isolated guinea-pig small intestine and some of its characteristics have been investigated. Depolarizing stimuli, i.e. elevation of the extracellular K+ concentration or electrical field stimulation, increased the release of I-SP, the extent of the increase being dependent on the strength of the stimulus. Omission of Ca2+ from the bath medium prevented the stimulus-induced release of I-SP. Tetrodotoxin inhibited only the increase in I-SP release brought about by electrical stimulation but not that caused by elevated K+ concentrations. Gel exclusion chromatography on Sephadex G-25 showed that all the I-SP released by depolarization was co-eluted with authentic substance P. The methionine enkephalin analogue FK 33-824 significantly reduced the stimulus-induced release of I-SP, an effect that was prevented by the opiate antagonist naloxone. Naloxone alone significantly enhanced the stimulus-induced release of I-SP, which suggests that endogenously released opioid peptides also exert an inhibitory action on myenteric substance P-containing neurons. Putative excitatory neurotransmitters of the myenteric plexus, such as acetylcholine, bombesin, cholecystokinin octapeptide, and neurotensin, stimulated the release of I-SP in a tetrodotoxin-sensitive manner, whereas 5-hydroxytryptamine seemed ineffective. Capsaicin, known to release substance P from sensory neurons, also failed to alter the release of I-SP. The finding of a Ca2+-dependent release of I-SP caused by depolarizing stimuli further supports the concept that substance P is a neurotransmitter within the myenteric plexus. The activity of myenteric substance P-containing neurons appears to be controlled by a number of other putative enteric neurotransmitters.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002211:Capsaicin / Q000494:pharmacology; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D008297:Male; D009197:Myenteric Plexus / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013373:Substance P / Q000378:metabolism*
D018377:Neurotransmitter Agents; D013373:Substance P; D009270:Naloxone; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D011188:Potassium; D002211:Capsaicin; D002118:Calcium