Similarities and differences between cardiac (H) and skeletal (S) muscle adenylate cyclase (AC) systems

131 SIMILARITIES AND DIFFERENCES BETWEEN CARDIAC (H) AND SKELETAL (S) MUSCLE ADENYLATE CYCLASE (AC) SYSTEMS. J.W. Wei, N. Narayanan and P.V. Sulakhe. Department of Physiology, University of Saskatchewan, College of Medicine, Saskatoon, Canada. Mn2+, compared to Mg2+, is substantially less effective in supporting catalytic activity of non-activated AC from S whereas it is equally or more effective for H-AC. And yet, the metal bindin sites of both Hand S-AC display much greater affinities towards Mn5+ compared to Mg2+. Following activation of S-AC by Gpp(NH)p (G) plus isoproterenol (ISO), Mn2+ becomes equally or more effective compared to Mg2+; activation caused by either IS0 or G alone does not impart maximal Mn2+-sensitivity. With either H- or S-AC, the apparent affinities of the metal binding sites towards Mg2+ and Mn2+ are significantly increased following activation of the enzyme by G alone or G plus ISO. Activation of AC from H and S by G or G plus IS0 does not significantly alter the respective apparent affinities of the catalytic site towards MgATP2- or MnATP2-. 'Ibeophylline causes non-specific inhibition of activated and non-activated AC from S but not from H. High Mg2+ inhibits non-activated S-AC but not H-AC. AC from H is readily inactivated by thermal denaturation and Mg2+ imparts greater lability, whereas AC from S is not readily inactivated and further, Mg2+ or Mn2+ imparts stability. Velocity obtained with saturating Mn2+ is further increased with Mg2+ for S-AC (but not H-AC) and this increase is not more than additive. (Supported by Sask. Heart Foundation and M.D.A.C.).

FLASMA LYSOSOMAL ENZYME ACTIVITY AFTER ACUTE MYOCARDIAL INFARCTION AND THE EFFECTS OF DRUGS. Elizabeth Welman, Cardiovascular Research Unit, Royal Postgraduate Medical School, London, England, Serial plasma samples were obtained from 65 patients suffering A control group of 45 uncomplicated acute myocardial infarction. patients received no therapeutic interventionsA group of 10 patients were established on beta-blocking drugs before the onset of myocardial infarction and were maintained on these drugs after A second group of IO patients received a admission to hospital. single intravenous infusion of methyl prednisolone sodium succinate (25 mg.kg'1) within 4h of the onset of chest pain. The patients in the control group all showed an increase in plasma lysosomal enzyme activity which was maximal at 18h after the onset of chest pain and correlated with the rise in creatine kinase In the groups of patients treated with activity (r = 0.98). either beta-blocking agents or methyl prednisolone the rise in plasma lysosomal enzyme activity was significantly delayed and reduced. These results are consistent with the experimental findings that such drugs can stabilize lyaosomal membranes during myocardial ischaemia. (Supported by a grant from the British Heart Foundation)