Adenyl cyclase activity in the perfused rat heart made to fail by substrate-lack.
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Biomedical subjects
Publications and source records attributed to N S Dhalla.
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1. Prostaglandin E(2) (PGE(2)) exerted positive cardiostimulant effects on isolated guinea-pig atria. The response was not altered by treatment of the animal with reserpine or by addition of propranolol to the organ bath. These results suggest that the cardiostimulatory actions of PGE(2) are not mediated through the release of catecholamines or stimulation of adrenoceptors.2. On the electrically driven atria, PGE(2) consistently exerted a cardiostimulant action which was not appreciably altered by changes in calcium ion in the bathing medium. PGE(2) showed no effect on the transport of calcium by the fragments of heart sarcoplasmic reticulum.3. PGE(2) reduced the responses to both noradrenaline and tyramine in the isolated atria. The shifted dose-response curve was not parallel to the original.4. PGE(2) increased the contractor response of the isolated vas deferens to nerve stimulation or to direct electrical stimulation.5. PGE(2) antagonized the increase caused by noradrenaline in contractor response of isolated vas deferens to direct electrical stimulation, whereas it affected the potentiation by noradrenaline differently when the vas deferens was contracting in response to nerve stimulation. In low concentration it inhibited and in large concentrations, it slightly enhanced the potentiation by catecholamine.6. It is concluded that PGE(2) has actions on multiple sites. It has post-junctional as well as pre-junctional effects on adrenergic neurones.
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1. A sarcolemmal fraction was isolated from hamster hind-leg skeletal muscles by successive treatment with lithium bromide and potassium chloride. The membranous fraction was observed to contain a highly active Ca(2+)-stimulated ATPase (adenosine triphosphatase), a Mg(2+)-stimulated ATPase, and an Na(+)+K(+)-stimulated Mg(2+)-dependent ouabain-sensitive ATPase. 2. The Ca(2+)-stimulated ATPase activity was pH-dependent, the optimum being pH7.6. 3. Optimum activation of this enzyme was obtained with 3-4mm-Ca(2+) when 4mm-ATP was present as a substrate, and was not influenced by Na(+), K(+) or ouabain, whereas 2,4-dinitrophenol, sodium azide, oligomycin, sodium fluoride and ethanedioxybis(ethylamine)tetra-acetate were inhibitory. 4. The Ca(2+)-stimulated ATPase was markedly inhibited by thiol-blocking reagents, and cysteine was able to reverse this inhibition. 5. Various bivalent cations stimulated ATP hydrolysis by the sarcolemmal fraction in the following decreasing order of potency: Mg(2+), Ca(2+), Mn(2+), Co(2+), Sr(2+), Ba(2+), Zn(2+), Cu(2+).
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