Carbachol-induced increase in inositol trisphosphate (IP3) content is attenuated by adrenergic stimulation in the isolated working rat heart.

The interrelated responses of concomitant adrenergic and muscarinic receptor stimulation on second messengers and mechanical activity in the isolated perfused working rat heart were studied. The hearts were perfused with Krebs-Henseleit buffer in a modified Langendorff apparatus. The hearts were perfused with noradrenaline (10(-6) mol L-1, n = 20), with carbachol (3 x 10(-7) mol L-1, n = 11) or with noradrenaline plus carbachol (n = 20) in the above-mentioned concentrations. The hearts were frozen at 20 s, 30 s and 40 min after addition of noradrenaline and noradrenaline plus carbachol and at 20 s and 40 min after addition of carbachol. Five hearts were freeze-clamped directly after preperfusion and another five hearts after 40 min of perfusion and used as controls. Myocardial cAMP increased at 20 s and 40 min after noradrenaline perfusion. In contrast to this cAMP was unchanged at 20 s and decreased at 40 min after perfusion with noradrenaline plus carbachol. IP3 content increased after 20 s of carbachol- and after 40 min of noradrenaline perfusion (P < 0.05). However, noradrenaline plus carbachol did not induced any significant increase in IP3 content after 20 s and 30 s, but after 40 min a decrease below basal level was found (P < 0.05). Noradrenaline stimulation attenuated muscarinic agonist induced IP3 formation. A reciprocity existed in that noradrenaline induced IP3 formation was attenuated by carbachol. No direct relationship was observed between the IP3 response and contractility, also valid for cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)