title: The beta-adrenergic receptor-regulated 1,4-dihydropyridine calcium channel receptor sites in coronary artery smooth muscle.
abstract: The cross-regulatory communication from beta-adrenergic receptors to 1,4-dihydropyridine (DHP) Ca2+ channel agonist and antagonist binding sites and cooperativity between DHP binding sites were studied in microsomal membranes of canine coronary artery (purified to a factor 2.9 for DHPs). The maximal number of binding sites (Bmax) identified in coronary artery microsomal membranes (CAM) with Ca2+ channel agonist (-)-S-(3H)BAY K 8644 was two times higher than Bmax of sites labelled with Ca2+ channel antagonist (+)-(3H)PN 200-110. The exposure of CAM to isoprenaline was accompanied with down-regulation of beta-adrenergic receptors and with increase in binding capacity for DHPs. The increase in Bmax was proportional in both groups of experiments and was related to increased affinity of DHPs. The 1,4-DHP binding sites identified in vascular smooth muscle showed characteristics typical for classification of specific 1,4-DHP receptor on Ca2+ channels. The binding was of high affinity, saturable and reversible, it showed stereoselectivity and it was positively modulated by beta-adrenergic stimulation and its showed cAMP and GTP sensitivity. The results support the hypothesis that beta-receptors also regulate the mode of Ca2+ channels in coronary artery smooth muscle.
authors.affiliation: Institute of Experimental Pharmacology, Slovak Academy of Sciences, Bratislava.
authors.forename: J
authors.initials: J
authors.lastname: Drímal
mesh_terms: D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004095:Dihydropyridines / Q000378:metabolism* / Q000494:pharmacology; D004285:Dogs; D006160:Guanosine Triphosphate / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D017275:Isradipine; D008297:Male; D008861:Microsomes / Q000648:ultrastructure; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D004095:Dihydropyridines; D011943:Receptors, Adrenergic, beta; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C038806:1,4-dihydropyridine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D007545:Isoproterenol; D017275:Isradipine