Presynaptic modulation by noradrenaline and an opioid of the substance P-induced release of [3H]acetylcholine from the myenteric plexus.
Substance P (7.5-750 nM) applied in superfusion dose-dependently released 3H from isolated strips of myenteric plexus-longitudinal muscle of the guinea-pig ileum loaded with [3H]choline. Separation of the [3H]acetylcholine and [3H]choline components of the released radioactivity revealed that in response to substance P (SP) administration only the release of [3H]acetylcholine increased above resting level. A slowly developing tachyphylaxis to the effect of SP was observed. Evidence has been obtained that the slow tachyphylaxis developed to the acetylcholine-releasing effect of SP was not due to the exhaustion of releasable acetylcholine pool. Release of acetylcholine by 150 nM SP was completely prevented by tetrodotoxin or in a Ca2+-free medium and greatly reduced in the presence of noradrenaline or the opioid receptor agonist (D-Met2,Pro5)-enkephalinamide. The effect of noradrenaline and the opioid peptide was apparently prevented by yohimbine and naloxone, respectively.
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D009197:Myenteric Plexus / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects; D013997:Time Factors
D013373:Substance P; D004744:Enkephalin, Methionine; C021717:enkephalin, Met(2)-ProNH2(5)-; D000109:Acetylcholine; D009638:Norepinephrine