Summary The properties of
1- and
2-adrenoceptors in right and left atria of rat heart, and their roles in mediating chronotropic and inotropic responses to
-adrenoceptor agonists were examined. [
125I](-)-pindolol (
125IPIN) bound saturably and specifically to a single class of high affinity sites in homogenates of both right and left atria. The
k
1's for association in right and left atria were 6.5×10
9 l/mol-min and 2.3×10
9 l/mol-min respectively, while the
k
–1's for dissociation were 0.20 min
–1 and 0.17 min
–1. The kinetically determined
K
D's were 75 pmol/l in right and 30 pmol/l in left atria and were similar to the equilibrium
K
D's determined from Scatchard analysis of saturation isotherms of specific
125IPIN binding. Inhibition of
125IPIN binding by
-adrenoceptor antagonists was stereoselective and the order of potency was timolol > 1-propranolol > d-propranolol > sotalol. Inhibition by
1- and
2-adrenoceptor subtype selective antagonists yielded flat displacement curves with low Hill coefficients. Nonlinear regression analysis of displacement by
1-selective (practolol, atenolol and metoprolol) and
2-selective (ICI 118,551) antagonists gave estimates of the proportion of
1- and
2-adrenoceptors present in rat atria. Right atria contained 67±4.2%
2-adrenoceptors and 33±4.2%
2-adrenoceptor, while left atria contained 67±2.8%
1- and 33±2.8%
2-adrenoceptors. Increases in the rate of spontaneously beating right atria and the force of electrically driven left atria caused by
-adrenoceptor agonists were also measured. pA
2 values for non-subtype selective
-adrenoceptor antagonists in inhibiting isoprenaline-induced increases in rate and force were highly correlated with
K
D values determined for specific
125IPIN binding. pA
2 values for
1- and
2-selective antagonists in inhibiting isoprenaline-induced increases in rate and force correlated well with the p
K
D values of these drugs in binding to
1-adrenoceptors, but not with the p
K
D values in binding to
2-adrenoceptors. Dose-response curves for stimulation of both rate and force by the
2-selective agonists procaterol and zinterol were shifted to a much greater extent by selective blockade of
1-adrenoceptors with metoprolol than by selective blockade of
2-adrenoceptors with ICI 118,551, suggesting that these compounds caused their effects by activating
1-adrenoceptors. These results suggest that
1- and
2-adrenoceptors coexist in both left and right atria of rat heart in approximately a 21 ratio, however only
1-adrenoceptors mediate the chronotropic and inotropic effects of
-adrenoceptor agonists.Supported by a grant from the American Heart Association — Georgia Affiliate
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