PHARMACOLOGICAL CHARACTERIZATION OF THE RECEPTORS INVOLVED IN THE BETA-ADRENOCEPTOR-MEDIATED STIMULATION OF THE L-TYPE CA2+ CURRENT IN FROGVENTRICULAR MYOCYTES

1 The whole-cell patch-clamp was used for studying the effects of vari ous beta(1)- and beta(2)-adrenoceptor agonists and antagonists on the L-type Ca current (I-Ca) in frog ventricular myocytes. 2 Dose-response curves for the effects of isoprenaline (non selective beta-agonist), salbutamol (beta(2)-agonist), dobutamine (beta(1)-agonist) on I-Ca wer e obtained in the absence and presence of various concentrations of IC T 118551 (beta(2)-antagonist), metoprolol (beta(1)-antagonist) and xam oterol (partial beta 1-agonist) to derive EC50 (i.e. the concentration of beta-agonist at which the response was 50% of the maximum) and E-m ax (the maximal response) values by use of a Michaelis equation. Schil d regression analysis was performed to examine whether the antagonists were competitive and to determine the equilibrium dissociation consta nt (K-B) for the antagonist-receptor complex. 3 Isoprenaline increased I-Ca with an EC50 of 20.0 nM and an E-max of 597%. ICI 118551 and met oprolol competitively antagonized the effect of isoprenaline with a K- B of 3.80 nM and 207 nM, respectively. 4 Salbutamol increased I-Ca wit h an EC50 of 290 nM and an E-max of 512%. ICI 118551 and metoprolol co mpetitively antagonized the effect of salbutamol with a K-B of 1.77 nM and 456 nM, respectively. 5 Dobutamine increased I-Ca with an EC50 of 2.40 mu M and an E-max of 265%. ICI 118551 and metoprolol competitive ly antagonized the effect of dobutamine with a K-B of 2.84 nM and 609 nM, respectively. 6 Xamoterol had no stimulating effect on I-Ca. Howev er, xamoterol competitively antagonized the stimulating effects of iso prenaline, salbutamol and dobutamine on I-Ca with a K-B of 58-64 nM. 7 We conclude that a single population of receptors is involved in the beta-adrenoceptor-mediated regulation of I-Ca in frog ventricular myoc ytes. The pharmacological pattern of the response of I-Ca to the diffe rent beta-adrenoceptor agonists and antagonists tested suggests that t hese receptors are of the beta(2)-subtype.