Abstract
We have recently described the preparation of a solubilized cat myocardial adenylate cyclase which is unresponsive to histamine, norepinephrine, glucagon, and thyroxine, the hormones which activate the particulate enzyme. Since hormone receptors may consist of proteins and phospholipids, we determined the effect of several phospholipids on restoring the responsiveness of the solubilized adenylate cyclase to histamine. The addition of phosphatidylserine completely restored the histamine-mediated activation of the solubilized enzyme in contrast to phosphatidylethanolamine and phosphatidylinositol which were without effect. The concentration of histamine producing half-maximal activation of adenylate cyclase, 2 × 10-5 M, was virtually identical with that observed in the particulate preparation. The antihistamine, diphenhydramine, 8 × 10-5 M, abolished activation of adenylate cyclase by histamine in both the solubilized and particulate preparations. Phosphatidylserine also restored glucagon responsiveness, but did not restore norepinephrine responsiveness. It would appear that phosphatidylserine produced the necessary molecular configuration of the adenylate cyclase for histamine binding and activation of the enzyme.
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- BARTLET A. L. THE ACTION OF HISTAMINE ON THE ISOLATED HEART. Br J Pharmacol Chemother. 1963 Dec;21:450–461. doi: 10.1111/j.1476-5381.1963.tb02013.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Birnbaumer L., Pohl S. L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. II. Comparison between glucagon- and fluoride-stimulated activities. J Biol Chem. 1971 Mar 25;246(6):1857–1860. [PubMed] [Google Scholar]
- Ehrenpreis S., Fleisch J. H., Mittag T. W. Approaches to the molecular nature of pharmacological receptors. Pharmacol Rev. 1969 Jun;21(2):131–181. [PubMed] [Google Scholar]
- Klein I., Levey G. S. Activation of myocardial adenyl cyclase by histamine in guinea pig, cat, and human heart. J Clin Invest. 1971 May;50(5):1012–1015. doi: 10.1172/JCI106571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Krishna G., Weiss B., Brodie B. B. A simple, sensitive method for the assay of adenyl cyclase. J Pharmacol Exp Ther. 1968 Oct;163(2):379–385. [PubMed] [Google Scholar]
- LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
- Levey G. S., Epstein S. E. Activation of adenyl cyclase by glucagon in cat and human heart. Circ Res. 1969 Feb;24(2):151–156. doi: 10.1161/01.res.24.2.151. [DOI] [PubMed] [Google Scholar]
- Levey G. S., Epstein S. E. Myocardial adenyl cyclase: activation by thyroid hormones and evidence for two adenyl cyclase systems. J Clin Invest. 1969 Sep;48(9):1663–1669. doi: 10.1172/JCI106131. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levey G. S. Restoration of glucagon responsiveness of solubilized myocardial adenyl cyclase by phosphatidylserine. Biochem Biophys Res Commun. 1971 Apr 2;43(1):108–113. doi: 10.1016/s0006-291x(71)80093-1. [DOI] [PubMed] [Google Scholar]
- Levey G. S. Restoration of norepinephrine responsiveness of solubilized myocardial adenylate cyclase by phosphatidylinositol. J Biol Chem. 1971 Dec 10;246(23):7405–7407. [PubMed] [Google Scholar]
- Levey G. S. Solubilization of myocardial adenyl cyclase. Biochem Biophys Res Commun. 1970 Jan 6;38(1):86–92. doi: 10.1016/0006-291x(70)91087-9. [DOI] [PubMed] [Google Scholar]
- Levey G. S. Solubilization of myocardial adenyl cyclase: less of hormone responsiveness and activation by phospholipids. Ann N Y Acad Sci. 1971 Dec 30;185:449–457. doi: 10.1111/j.1749-6632.1971.tb45272.x. [DOI] [PubMed] [Google Scholar]
- MURAD F., CHI Y. M., RALL T. W., SUTHERLAND E. W. Adenyl cyclase. III. The effect of catecholamines and choline esters on the formation of adenosine 3',5'-phosphate by preparations from cardiac muscle and liver. J Biol Chem. 1962 Apr;237:1233–1238. [PubMed] [Google Scholar]
- Pohl S. L., Krans H. M., Kozyreff V., Birnbaumer L., Rodbell M. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. VI. Evidence for a role of membrane lipids. J Biol Chem. 1971 Jul 25;246(14):4447–4454. [PubMed] [Google Scholar]
- Pöch G., Kukovetz W. R. Drug-induced release and pharmacodynamic effects of histamine in the guinea-pig heart. J Pharmacol Exp Ther. 1967 Jun;156(3):522–527. [PubMed] [Google Scholar]
- Rodbell M., Krans H. M., Pohl S. L., Birnbaumer L. The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. 3. Binding of glucagon: method of assay and specificity. J Biol Chem. 1971 Mar 25;246(6):1861–1871. [PubMed] [Google Scholar]
- SUTHERLAND E. W., RALL T. W., MENON T. Adenyl cylase. I. Distribution, preparation, and properties. J Biol Chem. 1962 Apr;237:1220–1227. [PubMed] [Google Scholar]
- TRENDELENBURG U. The action of histamine and 5-hydroxytryptamine on isolated mammalian atria. J Pharmacol Exp Ther. 1960 Dec;130:450–460. [PubMed] [Google Scholar]
- Waud D. R. Pharmacological receptors. Pharmacol Rev. 1968 Jun;20(2):49–88. [PubMed] [Google Scholar]


