ISSN:
1432-1912
Keywords:
Rat atrium
;
Inotropic response
;
Chronotropic response
;
β 1- andβ 2-adrenoceptors
;
Selectiveβ-adrenoceptor blocking drugs
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The properties ofβ 1- andβ 2-adrenoceptors in right and left atria of rat heart, and their roles in mediating chronotropic and inotropic responses toβ-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. Thek 1's for association in right and left atria were 6.5×109 l/mol-min and 2.3×109 l/mol-min respectively, while thek −1's for dissociation were 0.20 min−1 and 0.17 min−1. The kinetically determinedK D's were 75 pmol/l in right and 30 pmol/l in left atria and were similar to the equilibriumK D's determined from Scatchard analysis of saturation isotherms of specific125IPIN binding. Inhibition of125IPIN binding byβ-adrenoceptor antagonists was stereoselective and the order of potency was timolol 〉 1-propranolol 〉 d-propranolol 〉 sotalol. Inhibition byβ 1- andβ 2-adrenoceptor subtype selective antagonists yielded flat displacement curves with low Hill coefficients. Nonlinear regression analysis of displacement byβ 1-selective (practolol, atenolol and metoprolol) andβ 2-selective (ICI 118,551) antagonists gave estimates of the proportion ofβ 1- andβ 2-adrenoceptors present in rat atria. Right atria contained 67±4.2%β 2-adrenoceptors and 33±4.2%β 2-adrenoceptor, while left atria contained 67±2.8%β 1- and 33±2.8%β 2-adrenoceptors. Increases in the rate of spontaneously beating right atria and the force of electrically driven left atria caused byβ-adrenoceptor agonists were also measured. pA2 values for non-subtype selectiveβ-adrenoceptor antagonists in inhibiting isoprenaline-induced increases in rate and force were highly correlated withK D values determined for specific125IPIN binding. pA2 values forβ 1- andβ 2-selective antagonists in inhibiting isoprenaline-induced increases in rate and force correlated well with the pK D values of these drugs in binding toβ 1-adrenoceptors, but not with the pK D values in binding toβ 2-adrenoceptors. Dose-response curves for stimulation of both rate and force by theβ 2-selective agonists procaterol and zinterol were shifted to a much greater extent by selective blockade ofβ 1-adrenoceptors with metoprolol than by selective blockade ofβ 2-adrenoceptors with ICI 118,551, suggesting that these compounds caused their effects by activatingβ 1-adrenoceptors. These results suggest thatβ 1- andβ 2-adrenoceptors coexist in both left and right atria of rat heart in approximately a 2∶1 ratio, however onlyβ 1-adrenoceptors mediate the chronotropic and inotropic effects ofβ-adrenoceptor agonists.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00572434
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