Accumulation of inositol phosphates in sympathetic ganglia. Effects of depolarization and of amine and peptide neurotransmitters.
Depolarization of isolated [3H]inositol-labelled rat superior cervical sympathetic ganglia in a high-K+ medium stimulates an accumulation of labelled inositol phosphates. This accumulation occurs only when ganglia are incubated in a Ca2+-containing medium, suggesting that it represents a receptor-stimulated hydrolysis of inositol lipid(s) activated by an endogenously released neurotransmitter. A minor fraction of this accumulation appears to be activated by intraganglionically released acetylcholine, since it is slightly reduced by atropine. The accumulation of inositol phosphates is unaffected by blockade of appropriate catecholamine, histamine and 5-hydroxytryptamine receptors and also by aspirin and indomethacin. This response to depolarization is potentiated by incubation with proteinase inhibitors, suggesting that it might be caused by an endogenously released peptide neutrotransmitter. However, it is not prevented by a V1-vasopressin receptor antagonist, and none of the peptides tested so far fully reproduces the response: these include a stable substance P analogue, physalaemin, neurokinin alpha, bradykinin, angiotensin, pancreozymin, bombesin and luteinizing-hormone-releasing hormone. Stimulated inositol lipid breakdown in depolarized sympathetic ganglia seems likely to be activated by an as-yet-unidentified peptide neurotransmitter: this might serve as an intraganglionic mediator of postsynaptic excitation by employing the same signalling mechanism as muscarinic cholinergic and V1-vasopressin receptors.
Bone
E A
EA
Michell
R H
RH
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D009116:Muscarine / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013403:Sugar Phosphates / Q000378:metabolism*
D001626:Bethanechol Compounds; D007295:Inositol Phosphates; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D011480:Protease Inhibitors; D013403:Sugar Phosphates; D018723:Bethanechol; D001285:Atropine; D009116:Muscarine; D011188:Potassium; D002118:Calcium