Ingerebretsen_1977_Circ.Res_40_474

The effects of (-)-isoproterenol covalently linked to glass beads on inotropic state, cyclic AMP concentration, and phosphorylase b to a conversion was studied in cat and guinea pig papillary muscles. Biochemical responses also were measured in mouse diaphragm sections. In cat papillary muscles under normal conditions and in guinea pig muscles partly depolarized with 22 mM K+ an increased inotropic state and phosphorylase activation could be dissociated from the formation of cyclic AMP. This contrasts with close correlation reported between isometric tension and cyclic AMP concentration in guinea pig papillary muscles exposed to varying concentrations of isoproterenol dissolved in the bath medium. The cyclic nucleotide did increase in guinea pig papillary muscles exposed to a freshly prepared batch of isoproterenol beads and in the mouse diaphragms. The type and age of the bead preparation had marked effects on all responses that were measured and on the rate of leakage of biologically active products from the beads. Nevertheless, experimental conditions could be obtained under which the initiation of the contractile and biochemical responses was probably limited to intense stimulation of receptors at or near the points of contact between beads and muscle and not due to gross leakage into the bath. The results indicate that cyclic AMP is probably involved in the initiation but not the propagation of the inotropic response of papillary muscles exposed to isoproterenol glass beads.