Stimulation of phosphoinositide hydrolysis and inhibition of cyclic AMP formation by muscarinic agonists in developing chick heart.

As early as 4 days in ovo, phosphoinositide hydrolysis in embryonic chick heart was stimulated by the cholinergic agonist carbachol. In the 4-day chick heart, the concentrations of carbachol giving half-maximal and maximal stimulation of [3H]inositol 1-phosphate formation were 30 microM and 1 mM respectively. These values are identical to those obtained using hearts from 13-day embryos [J. H. Brown and S. L. Brown, J. biol. Chem. 259, 3777 (1984)]. The amounts of [3H]inositol 1-phosphate formed per mg protein in the presence of carbachol were greater at early ages than at later ones; the stimulation by carbachol thus decreased from 8-fold at 4 days to 2-fold at 13 days. Muscarinic receptor stimulation also led to inhibition of isoproterenol-stimulated cyclic AMP formation as early as 4 days. The isoproterenol-stimulated increase in cyclic AMP was greatest at early ages, whereas the inhibitory effect of carbachol remained constant at 75%. At 4 days, half-maximal and maximal inhibition by carbachol occurred at 0.3 and 30 microM, respectively, the same values obtained using 13-day hearts (see reference cited above). Thus, the two biochemical responses of embryonic chick heart to muscarinic agonists have identical agonist sensitivities regardless of embryonic age and are functional prior to parasympathetic innervation and physiological responsiveness.