Inhibitory effect of octopamine on the release of endogenous acetylcholine from isolated myenteric synaptosomes of guinea-pig.
1. The effect of octopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal preparations of guinea-pigs was examined using high pressure liquid chromatography with electrochemical detection. Release of ACh was induced by substance P or by depolarization with high potassium (50 mmol/L) in medium containing atropine, propranolol and naloxone. 2. Octopamine produced a dose-dependent inhibition of substance P-induced ACh release. A similar inhibitory action of octopamine was found in the samples depolarized by high potassium as a reference. 3. The action of octopamine was not reversed by the dopamine receptor antagonists either for the DA-2 subtype, domperidone, or for the DA-1 subtype, SCH23390, or by haloperidol. However, idazoxan and yohimbine antagonized this octopamine-induced inhibition at concentrations sufficient to abolish the action of clonidine. 4. Failure of guanethidine or nomifensine to inhibit octopamine ruled out mediation by noradrenergic neurotransmitters. 5. Octopamine decreased the influx of [45Ca] stimulated by substance P into synaptosomal preparations and this was reversed by idazoxan or yohimbine at concentrations sufficient to block the action of clonidine. 6. Pertussis toxin abolished the inhibitory action of octopamine at a dose high enough to block the action of clonidine. 7. These results indicate that octopamine suppresses the influx of calcium ions into cholinergic nerve terminals of ileal synaptosomes of guinea-pigs via an activation of alpha 2-adrenoceptors coupled with a pertussis toxin-sensitive GTP-binding protein which results in a decrease of ACh release.
Chang
S S
SS
Department of Nursing Sciences, Chinese Junior College of Medical Technology, Tainan.
Cheng
J T
JT
D000109:Acetylcholine / Q000378:metabolism*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015259:Dopamine Agents / Q000037:antagonists & inhibitors; D005260:Female; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation; D066298:In Vitro Techniques; D008297:Male; D009197:Myenteric Plexus / Q000187:drug effects* / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D009655:Octopamine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism
D000317:Adrenergic alpha-Antagonists; D015259:Dopamine Agents; D009655:Octopamine; D009627:Nomifensine; D013373:Substance P; D009270:Naloxone; D001285:Atropine; D011433:Propranolol; D000109:Acetylcholine; D002118:Calcium; D006145:Guanethidine