Inhibitory Effect of Octopamine on the Release of Endogenous Acetylcholine From Isolated Myenteric Synaptosomes of Guinea‐pig

Abstract

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.

Dopamine‐induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea‐pig mediated via α‐adrenoceptors

“…Also, in order to rule out the participation of muscarinic autoregulation (Kilbinger & Nafziger, 1985), atropine was added to the incubating buffer in this experiment. Like our previous finding (Chang & Cheng, 1994), substance P or high potassium depolarization can be used to stimulate the release of endogenous ACh. Dopamine attenuated the release of endogenous ACh in a concentration-dependent manner and a parallel blockade was found between the substance P-induced samples and the high potassium depolarized synaptosomes.…”

Simulatory effect of porcine insulin on noradrenaline secretion in guinea‐pig ileum myenteric nerve terminals

“…The segment midway between stomach and ileo‐caecal junction (20–25 cm) was dissected from the mesentery and then removed from the animal. A crude synaptosomal fraction was prepared according to our previously described method (Chang & Cheng, 1993). In brief, the minced tissues of the longitudinal muscle strips, prepared as described previously (Paton & Zar, 1968), were homogenized in 0.32 m sucrose‐phosphate buffer at 5 ml g –1 wet wt.…”