Norepinephrine-stimulated PI hydrolysis in oligodendrocytes is mediated by alpha 1A-adrenoceptors.
Oligodendrocyte progenitors were labelled with [3H]-myo-inositol in order to determine the effect of adrenergic agents on the accumulation of [3H]-inositol phosphates (InsP). Both norepinephrine and phenylephrine, a selective alpha 1-adrenoceptor agonist, increased the formation of [3H]-InsP, while isoproterenol, a beta-adrenoceptor agonist, did not. Propranolol (beta) and yohimbine (alpha 2), two adrenoceptor antagonists, had no significant effect on the NE-stimulated [3H]-InsP formation. By contrast, the response to NE was significantly blocked by phenoxybenzamine and the alpha 1-receptor antagonist, prazosin. Pretreatment with chloroethylclonidine, which selectively inactivates alpha 1B receptors, had no effect on NE-induced [3H]-InsP formation, while WB4101 had high potency in inhibiting this response. Pertussis toxin, which inactivates certain G-proteins, caused a approximately 60% reduction. NE-stimulated formation of [3H]-InsP depended on extracellular calcium influx, because it was decreased by 55% and 75% by chelation with EGTA or the addition of 1 mM CdCl2, respectively. These results suggest that oligodendrocyte progenitors express alpha 1-adrenoceptors characteristic of the alpha 1A subtype.
Cohen
R I
RI
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada.
Almazan
G
G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000096:biosynthesis; D019204:GTP-Binding Proteins / Q000378:metabolism; D006868:Hydrolysis; D009638:Norepinephrine / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D010716:Phosphatidylinositols; D018340:Receptors, Adrenergic, alpha-1; D010566:Virulence Factors, Bordetella; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D002118:Calcium; D009638:Norepinephrine