INHIBITION OF S-ADENOSYL-L-HOMOCYSTEINE HYDROLASE BY ADRENALINE IN ISOLATED GUINEA-PIG PAPILLARY-MUSCLES

Purified S-adenosyl-L-homocysteine hydrolase from Dictyostelium discoi deum or rabbit erythrocytes is inactivated when incubated with cAMP, T he aim of this study was to investigate whether adrenaline, which incr eases cytosolic cAMP and calcium concentrations, is able to modify in situ the activity of S-adenosyl-L-homocysteine hydrolase in the heart. The enzyme was assayed in a crude extract obtained from superfused gu inea-pig papillary muscles with the different tested substances. Adren aline was found to inhibit S-adenosyl-L-homocysteine hydrolase in papi llary muscles in a concentration-dependent fashion. This inhibition wa s associated with an increase in the concentration of S-adenosyl-L-hom ocysteine (326%), and a decrease of adenosine (40%), beta-Adrenoceptor s are involved in the effect of adrenaline, since isoproterenol, a bet a-adrenergic agonist, inhibited the enzyme, whereas the beta-adrenergi c blocker, propranolol, prevented this inhibition, Participation of ca lcium in the inhibitory effect of adrenaline was suggested because the calcium channel blocker, verapamil, suppressed this inhibition, and h igh calcium in the perfusion medium inhibited the enzyme. In vitro exp eriments with calcium were performed in a semi-purified fraction of th e enzyme, resulting in a concentration-dependent inhibition of the enz yme, Calcium concentration, which inhibited the enzyme 50%, was in the millimolar range for control and in the micromolar range for the obta ined enzyme from adrenaline-treated muscles, indicating a different se nsitivity to calcium inhibition, We conclude that adrenaline inhibits S-adenosyl-L-homocysteine-hydrolase in situ, probably by a calcium-mod ulated mechanism. (C) 1997 Published by Elsevier Science Ltd. All righ ts reserved.