Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Feb;111(2):539–546. doi: 10.1111/j.1476-5381.1994.tb14771.x

Functional studies on alpha 1-adrenoceptor subtypes mediating inotropic effects in rat right ventricle.

M C Michel 1, G Hanft 1, G Gross 1
PMCID: PMC1909968  PMID: 7911719

Abstract

1. We have studied the alpha 1-adrenoceptor subtypes mediating inotropic effects of adrenaline in rat right ventricle and the Ca2+ sources used to elicit these effects. alpha 1A-Adrenoceptor-mediated contractile effects in rat vas deferens were studied for comparison in some cases. 2. Treatment with chloroethylclonidine did not affect the maximal beta-adrenoceptor-mediated inotropic effects in rat right ventricle or the maximal alpha 1A-adrenoceptor-mediated contractile effects in rat vas deferens; it did not alter the potency of isoprenaline in the ventricle and reduced the potency of the alpha-adrenoceptor antagonists in vas deferens only slightly. Treatment of right ventricular strips with CdCl2 markedly reduced resting tension and enhanced maximal inotropic effects of isoprenaline but did not affect its potency. 3. Inactivation of cardiac alpha 1B-adrenoceptors by treatment with chloroethylclonidine slightly enhanced the maximal inotropic effects of the full agonist, adrenaline and of several partial agonists. 4. Schild analysis of inhibition experiments with the alpha 1A-adrenoceptor-selective antagonists, 5-methyl-urapidil and (+/-)-tamsulosin, demonstrated that adrenaline causes its inotropic effects mainly via the alpha 1B-adrenoceptor subtype. Schild analysis of 5-methyl-urapidil inhibition experiments in chloroethylclonidine-treated ventricles indicated that only alpha 1A-adrenoceptors mediate the inotropic effects of adrenaline following inactivation of the alpha 1B-adrenoceptors. 5. In control ventricles the organic Ca2+ entry blocker, nitrendipine and treatment with the inorganic Ca2+ entry blocker, CdCl2 did not reduce inotropic effects of adrenaline whereas ryanodine treatment inhibited them. In contrast, nitrendipine and CdCl2 treatment had major inhibitory effects in chloroethylclonidine-treated but lacked inhibitory effects in phenoxybenzamine-treated ventricular strips. 6. We conclude that inotropic effects of adrenaline in rat heart are mediated mainly by alpha 1B-adrenoceptors via release of Ca2+ from an intracellular pool.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
539

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anyukhovsky E. P., Rosen M. R. Abnormal automatic rhythms in ischemic Purkinje fibers are modulated by a specific alpha 1-adrenergic receptor subtype. Circulation. 1991 Jun;83(6):2076–2082. doi: 10.1161/01.cir.83.6.2076. [DOI] [PubMed] [Google Scholar]
  3. Beckeringh J. J., Thoolen M. J., de Jonge A., Wilffert B., Timmermans P. B., van Zwieten P. A. Differential effects of the calcium entry blocker D 600 on contractions of rat and guinea-pig aortas, elicited by various alpha-1 adrenoceptor agonists. J Pharmacol Exp Ther. 1984 May;229(2):515–521. [PubMed] [Google Scholar]
  4. Benfey B. G. Function of myocardial alpha-adrenoceptors. Life Sci. 1990;46(11):743–757. doi: 10.1016/0024-3205(90)90062-v. [DOI] [PubMed] [Google Scholar]
  5. Brodde O. E., Michel M. C. Adrenergic receptors and their signal transduction mechanisms in hypertension. J Hypertens Suppl. 1992 Dec;10(7):S133–S145. [PubMed] [Google Scholar]
  6. Bylund D. B. Subtypes of alpha 1- and alpha 2-adrenergic receptors. FASEB J. 1992 Feb 1;6(3):832–839. doi: 10.1096/fasebj.6.3.1346768. [DOI] [PubMed] [Google Scholar]
  7. Goa K. L., Sorkin E. M. Nitrendipine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in the treatment of hypertension. Drugs. 1987 Feb;33(2):123–155. doi: 10.2165/00003495-198733020-00003. [DOI] [PubMed] [Google Scholar]
  8. Gross G., Hanft G., Rugevics C. U. Alpha 1-adrenoceptors of rat myocardium: comparison of agonist binding and positive inotropic response. Naunyn Schmiedebergs Arch Pharmacol. 1988 Nov;338(5):582–588. doi: 10.1007/BF00179334. [DOI] [PubMed] [Google Scholar]
  9. Han C. D., Minneman K. P. Interaction of subtype-selective antagonists with alpha 1-adrenergic receptor binding sites in rat tissues. Mol Pharmacol. 1991 Oct;40(4):531–538. [PubMed] [Google Scholar]
  10. Han C., Abel P. W., Minneman K. P. Alpha 1-adrenoceptor subtypes linked to different mechanisms for increasing intracellular Ca2+ in smooth muscle. Nature. 1987 Sep 24;329(6137):333–335. doi: 10.1038/329333a0. [DOI] [PubMed] [Google Scholar]
  11. Hanft G., Gross G., Beckeringh J. J., Korstanje C. Alpha 1-adrenoceptors: the ability of various agonists and antagonists to discriminate between two distinct [3H]prazosin binding sites. J Pharm Pharmacol. 1989 Oct;41(10):714–716. doi: 10.1111/j.2042-7158.1989.tb06348.x. [DOI] [PubMed] [Google Scholar]
  12. Hanft G., Gross G. Subclassification of alpha 1-adrenoceptor recognition sites by urapidil derivatives and other selective antagonists. Br J Pharmacol. 1989 Jul;97(3):691–700. doi: 10.1111/j.1476-5381.1989.tb12005.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hilton P. J. Cellular sodium transport in essential hypertension. N Engl J Med. 1986 Jan 23;314(4):222–229. doi: 10.1056/NEJM198601233140407. [DOI] [PubMed] [Google Scholar]
  14. Knowlton K. U., Michel M. C., Itani M., Shubeita H. E., Ishihara K., Brown J. H., Chien K. R. The alpha 1A-adrenergic receptor subtype mediates biochemical, molecular, and morphologic features of cultured myocardial cell hypertrophy. J Biol Chem. 1993 Jul 25;268(21):15374–15380. [PubMed] [Google Scholar]
  15. Langer G. A. Calcium and the heart: exchange at the tissue, cell, and organelle levels. FASEB J. 1992 Feb 1;6(3):893–902. doi: 10.1096/fasebj.6.3.1310947. [DOI] [PubMed] [Google Scholar]
  16. Lomasney J. W., Cotecchia S., Lefkowitz R. J., Caron M. G. Molecular biology of alpha-adrenergic receptors: implications for receptor classification and for structure-function relationships. Biochim Biophys Acta. 1991 Oct 26;1095(2):127–139. doi: 10.1016/0167-4889(91)90075-9. [DOI] [PubMed] [Google Scholar]
  17. Michel M. C., Büscher R., Kerker J., Kraneis H., Erdbrügger W., Brodde O. E. Alpha 1-adrenoceptor subtype affinities of drugs for the treatment of prostatic hypertrophy. Evidence for heterogeneity of chloroethylclonidine-resistant rat renal alpha 1-adrenoceptor. Naunyn Schmiedebergs Arch Pharmacol. 1993 Oct;348(4):385–395. doi: 10.1007/BF00171338. [DOI] [PubMed] [Google Scholar]
  18. Michel M. C., Hanft G., Gross G. Radioligand binding studies of alpha 1-adrenoceptor subtypes in rat heart. Br J Pharmacol. 1994 Feb;111(2):533–538. doi: 10.1111/j.1476-5381.1994.tb14770.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Minneman K. P. Alpha 1-adrenergic receptor subtypes, inositol phosphates, and sources of cell Ca2+. Pharmacol Rev. 1988 Jun;40(2):87–119. [PubMed] [Google Scholar]
  20. Minneman K. P., Han C., Abel P. W. Comparison of alpha 1-adrenergic receptor subtypes distinguished by chlorethylclonidine and WB 4101. Mol Pharmacol. 1988 May;33(5):509–514. [PubMed] [Google Scholar]
  21. Otsu K., Willard H. F., Khanna V. K., Zorzato F., Green N. M., MacLennan D. H. Molecular cloning of cDNA encoding the Ca2+ release channel (ryanodine receptor) of rabbit cardiac muscle sarcoplasmic reticulum. J Biol Chem. 1990 Aug 15;265(23):13472–13483. [PubMed] [Google Scholar]
  22. Pucéat M., Terzic A., Clément O., Scamps F., Vogel S. M., Vassort G. Cardiac alpha 1-adrenoceptors mediate positive inotropy via myofibrillar sensitization. Trends Pharmacol Sci. 1992 Jul;13(7):263–265. doi: 10.1016/0165-6147(92)90080-p. [DOI] [PubMed] [Google Scholar]
  23. Ruffolo R. R., Jr, Nichols A. J., Stadel J. M., Hieble J. P. Structure and function of alpha-adrenoceptors. Pharmacol Rev. 1991 Dec;43(4):475–505. [PubMed] [Google Scholar]
  24. Stern M. D., Lakatta E. G. Excitation-contraction coupling in the heart: the state of the question. FASEB J. 1992 Sep;6(12):3092–3100. doi: 10.1096/fasebj.6.12.1325933. [DOI] [PubMed] [Google Scholar]
  25. Takanashi M., Norota I., Endoh M. Potent inhibitory action of chlorethylclonidine on the positive inotropic effect and phosphoinositide hydrolysis mediated via myocardial alpha 1-adrenoceptors in the rabbit ventricular myocardium. Naunyn Schmiedebergs Arch Pharmacol. 1991 Jun;343(6):669–673. doi: 10.1007/BF00184301. [DOI] [PubMed] [Google Scholar]
  26. Wang X. L., Wettwer E., Gross G., Ravens U. Reduction of cardiac outward currents by alpha-1 adrenoceptor stimulation: a subtype-specific effect? J Pharmacol Exp Ther. 1991 Nov;259(2):783–788. [PubMed] [Google Scholar]
  27. Wilson K. M., Minneman K. P. Different pathways of [3H]inositol phosphate formation mediated by alpha 1a- and alpha 1b-adrenergic receptors. J Biol Chem. 1990 Oct 15;265(29):17601–17606. [PubMed] [Google Scholar]
  28. del Balzo U., Rosen M. R., Malfatto G., Kaplan L. M., Steinberg S. F. Specific alpha 1-adrenergic receptor subtypes modulate catecholamine-induced increases and decreases in ventricular automaticity. Circ Res. 1990 Dec;67(6):1535–1551. doi: 10.1161/01.res.67.6.1535. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES