The sigma compounds 1,3-di-o-tolylguanidine and N-allylnormetazocine inhibit agonist-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells.
Muscarine stimulated a concentration-dependent accumulation of [3H]inositol phosphates in bovine adrenal medullary cells preloaded with [3H]inositol. This muscarinic activation of inositol phospholipid metabolism was fully inhibited by the sigma-ligand 1,3-di-o-tolylguanidine (DTG) with an IC50 of approximately 45 microM. Higher concentrations (100 microM) of (+) N-allylnormetazocine (SKF-10047) also partially inhibited this response. A concentration of DTG sufficient to fully inhibit the muscarinic response also produced a significant partial inhibition of [3H]inositol phosphate accumulation in response to histamine but not to angiotensin II. These data demonstrate that sigma-compounds inhibit agonist-stimulated inositol phospholipid metabolism in bovine adrenal medullary cells, with a degree of selectivity towards the muscarinic response.
Bunn
S J
SJ
Neuroscience Group, Faculty of Medicine, University of Newcastle, Callaghan, NSW, Australia.
Brent
P J
PJ
O'Malley
S R
SR
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007700:Kinetics; D009116:Muscarine / Q000494:pharmacology*; D010620:Phenazocine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D014316:Tritium
D000927:Anticonvulsants; D006146:Guanidines; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D014316:Tritium; D000804:Angiotensin II; D007294:Inositol; C012134:SK&F 10047; D009116:Muscarine; D006632:Histamine; D010620:Phenazocine; C050232:1,3-ditolylguanidine