Cholera toxin accentuates the antagonism by acetylcholine of higenamine-induced positive chronotropy is isolated right atria of mice

Biological & Pharmaceutical Bulletin
I KimuraM Kimura

Abstract

+/- -Higenamine (demethylcoclaurine), a cardiotonic principle from aconite root, chronotropic and inotropic actions mediated through beta 1-adrenergic receptors. We have investigated the influence of cholera toxin (CTX), a Gs-protein activator, and pertussis toxin (PTX), a Gi-protein inhibitor on the chronotropic interaction between higenamine and a muscarinic agonist, acetylcholine (ACh) in the isolated right atria of mice. CTX (100nm, 1h) pretreatment accentuated the inhibitory responses to cumulative applications of ACh (30nM--30 microns for the positive chronotropic effects induced by higenamine (100nM), isoproterenol (3 and 10 nM) or dobutamine (100nM). In normal atria (CTX-untreated), ACh physiologically antagonized the positive chronotropic effects of these beta-adrenergic agonists. Pretreatment with PTX (150 microgram/kg, i.p., 3d) abolished the CTX (100nm, 1 h)-induced accentuation in the inhibitory effect of ACh against higenamine. PTX pretreatment also attenuated the physiological antagonism by ACh against higenamine in normal atria. The negative chronotropic effect of ACh was not affected by a submaximal concentration of forskolin (1 micron). The These results suggest an accentuated antagonism between higenamine and...Continue Reading

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.