Platelet-activating factor mediated potentiation of stimulation-evoked catecholamine release and the rise in intracellular free Ca2+ concentration in adrenal chromaffin cells.
The effects of platelet-activating factor (PAF) on catecholamine (CA) release and intracellular free Ca2+ concentration ([Ca2+]i) were studied in cultured bovine adrenal chromaffin cells. PAF (1 nM-1 micron) alone had no effect on [Ca2+]i and basal CA release, but potentiated the [Ca2+]i rise and CA release evoked by acetylcholine (ACh) and by elevated extracellular K+. PAF did not potentiate the responses to caffeine in Ca(2+)-deficient medium or to Bay K 8644. In chromaffin cells pretreated with either BN 50739, tetrodotoxin and amiloride or in Na(+)-deficient medium, PAF failed to potentiate the stimulation-evoked [Ca2+]i rise and CA release. In contrast, neomycin, U 73122, 5-(N-ethyl-N-isopropyl)amiloride or pertussis toxin were ineffective in blocking the potentiating effect of PAF. In a membrane fraction prepared from fresh bovine adrenal medulla, ligand-binding studies using [3H]WEB 2086 identified a PAF-displaceable binding site. These results are consistent with a model in which PAF modulates CA release by activating plasma membrane receptors that can enhance the [Ca2+]i rise via an Na(+)-dependent mechanism.
Morita
K
K
Department of Pharmacology, Hiroshima University School of Dentistry, Japan.
Suemitsu
T
T
Uchiyama
Y
Y
Miyasako
T
T
Dohi
T
T
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000311:Adrenal Glands / Q000166:cytology; D000818:Animals; D001381:Azepines / Q000378:metabolism; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007700:Kinetics; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D013268:Stimulation, Chemical; D013997:Time Factors; D014230:Triazoles / Q000378:metabolism
D001381:Azepines; D002395:Catecholamines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014230:Triazoles; C039351:platelet activating factor receptor; C052518:WEB 2086; D002110:Caffeine; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000109:Acetylcholine; D002118:Calcium