THE BETA-ADRENERGIC RECEPTOR-REGULATED 1,4-DIHYDROPYRIDINE CALCIUM-CHANNEL RECEPTOR-SITES IN CORONARY-ARTERY SMOOTH-MUSCLE

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 (B(max)) identified in coronary artery microsomal membranes (CAM) with Ca2+ channel agonist (-)-S-(H-3)BAY K 8644 was two times higher than B(max) of sites labelled with Ca2+ channel antagonist (+)-(H-3)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 B(max) 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 it 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.