Muscarinic stimulation of cardiac guanylate cyclase

Right ventricular kitten papillary muscles were incubated with dibutyryl adenosine 3',5'-monophosphate (db-cAMP) at varying concentrations from 1 X 10(-4) M to 1 X 10(-3) M. A positive inotropic effect was observed with all concentrations of db-cAMP. Concomitant administration of 5 X 10(-4) M monobutyryl guanosine 3',5'-monophosphate and 1--2 X 10(-4) M db-cAMP did not produce an inotropic response. At the biochemical level cardiac guanyl cyclase activity is enhanced 2--3 times with acetylcholine and this enhancement is completely blocked by atropine. This increased activity appears to be the result of a decrease in the Michaelis constant (Km) for GTP. Calcium also produces a significant activation of guanyl cyclase activity.