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J G Dobson

Publications and source records attributed to J G Dobson.

64 records · Page 4Linked to original sources
PubMed1976

The role of cyclic adenosine 3', 5'-monophosphate and calcium in the regulation of contractility and glycogen phosphorylase activity in guinea pig papillary muscle.

We studied the relationships between the positive inotropic effects of isoproterenol, increased frequency of contraction or paired electrical stimulation, and cyclic AMP concentration and phosphorylase activity in isolated guinea pig papillary muscles. The minimum concentration of isoproterenol (10 nM) that augmented isometric force development increased cyclic AMP concentration. However 100 nM isoproterenol was required to increase the phosphorylase activity ratio (-AMP/+AMP) from 0.15 +/- 0.03 to 0.25 +/- 0.03. After addition of 1 muM isoproterenol to the bath, cyclic AMP increased within 0.5 minute from 0.58 +/- 0.03 to 1.04 +/- 0.13 mol/kg (wet weight), peak contractile force was elevated 2-fold at 1 minute, and the phosphorylase activity ratio rose to 0.40 +/- 0.02 in 4 minutes. Although an increase in contraction frequency (6/min to 36/ min) and paired stimulation produced more than a 3-fold increase in peak contractile force, there were no changes in cyclic AMP and phosphorylase activity. The cyclic AMP concentration during diastole was 0.60 +/- 0.04 and in midsystole, 0.55 +/- 0.03 mumol/kg. Anoxia increased the phosphorylase activity ratio from 0.19 +/-0.02 to 0.41 +/- 0.04 without elevation of cyclic AMP concentration. Removal of Ca2+ from the bathing medium prevented active force development and the anoxic increase in phosphorylase activity, but did not prevent the isoproterenol-induced increase in cyclic AMP and phosphorylase. These results suggest that cyclic AMP is a factor in the catecholamine-induced enhancement of inotropic state. However, it does not appear to play a role in the maintained augmentation of inotropic state produced by increased contraction frequency and paired stimulation, nor does the concentration of the cycle nucleotide appear to vary during the contraction cycle or during anoxia. Extracellular Ca2+ is required for contraction, the positive inotropic aciton of catecholamines and phosphorylase b to a conversion by anoxia.

Animals↗
PubMed1975

Dissociations between changes in myocardial cyclic adenosine monophosphate and contractility.

The relationship between changes in the myocardial concentration of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and cardiac contractility was studied in guinea pig and rat myocardium. When isolated perfused guinea pig heart were perfused with 10-5-M papaverine, a potent inhibitor of cyclic AMP phosphodiesterase activity, myocardial cyclic AMP concentration increased significantly from 1.7 plus and minus 0.2 (SE) pmoles/mg protein (N equal 12) to 3.3 plus and minus 0.2 pmoles/mg protein (N equal 12), and the percent of phosphorylase aual 6) (P less than 0.01). However, perfusion with papaverine had no effect on contractility in the absence or the presence of exogenous epinephrine. In perfused rat hearts, 10-5 M glucagon increased myocardial cyclic AMP concentration from 1.5 plus and minus 0.1 pmoles/mg protein (N equal 12) to 2.6 plus and minus 0.1 pmoles/mg protein (N equal 12) (P less than 0.001). In contrast, cyclic AMP levels did not increase detectably in guinea pig heart perfused with glucagon. Glucagon increased adenylate cyclase activity more than twofold in rat myocardial broken cell preparations but failed to stimulate the enzyme in preparations from guinea pigs. Despite these differences, the positive inotropic effects of glucagon on rat and guinea pig hearts were very similar over a wide dose range. Thus, with both papaverine and glucagon, changes in cardiac contractility were dissociated from stimulation of adenylate cyclase activity, increases in myocardial cyclic AMP levels, and conversion of phosphorylase b to phosphorylase a in perfused hearts.

Adenylyl Cyclases↗