PHARMACOLOGICAL CHARACTERIZATION OF THE RECEPTORS INVOLVED IN THE BETA-ADRENOCEPTOR-MEDIATED STIMULATION OF THE L-TYPE CA2+ CURRENT IN FROGVENTRICULAR MYOCYTES
Va. Skeberdis et al., PHARMACOLOGICAL CHARACTERIZATION OF THE RECEPTORS INVOLVED IN THE BETA-ADRENOCEPTOR-MEDIATED STIMULATION OF THE L-TYPE CA2+ CURRENT IN FROGVENTRICULAR MYOCYTES, British Journal of Pharmacology, 121(7), 1997, pp. 1277-1286
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.