This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Shibata, K. Articles by Tsujimoto, G. Search for Related Content PubMed PubMed Citation Articles by Shibata, K. Articles by Tsujimoto, G.

(Circulation. 1998;97:1227-1230.)
© 1998 American Heart Association, Inc.

Brief Rapid Communications

Effects of Quinidine and Verapamil on Human Cardiovascular ₁-Adrenoceptors

Katsushi Shibata, MD; Akira Hirasawa, PhD; Rudolf Foglar, MD, PhD; Satoshi Ogawa, MD, PhD; ; Gozoh Tsujimoto, MD, PhD

From the Department of Molecular Cell Pharmacology, National Children's Medical Research Center (A.H., R.F., G.T.), and the Department of Internal Medicine, School of Medicine, Keio University (K.S., S.O.), Tokyo, Japan.

Correspondence to Gozoh Tsujimoto, MD, PhD, Department of Molecular Cell Pharmacology, National Children's Medical Research Center, 3–35-31 Taishido, Setagaya-ku, Tokyo, Japan 154. E-mail gtsujimoto{at}nch.go.jp

Background—The antiarrhythmic drugs quinidine and verapamil are known to block ₁-adrenoceptors (₁ARs). ₁ARs are a heterogeneous family of three subtypes (_1A, _1B, and _1D), and little is known about the effects of quinidine and verapamil on the different human ₁AR subtypes.

Methods and Results—Reverse transcriptase–polymerase chain reaction showed that all ₁AR subtypes are expressed in both human heart (atrium and ventricle) and the mesenteric artery. Pharmacological profiles of quinidine and verapamil actions on the ₁AR subtypes were characterized with Chinese hamster ovary cells stably expressing cloned human ₁AR subtypes. Radioligand binding studies showed that quinidine and verapamil had high affinities for all ₁AR subtypes. Also, both drugs synergistically inhibited ₁AR-mediated inositol 1,4,5-triphosphate production at the clinical effective concentration range (1 µmol/L quinidine and 0.1 µmol/L verapamil).

Conclusions—The results show that all ₁AR subtypes are expressed in the human cardiovascular system and that quinidine and verapamil may have a potent, synergistic inhibitory effect on the ₁ARs. Clinically observed hypotension after quinidine plus verapamil can be explained by their synergistic inhibitory effects on human ₁ARs.

Key Words: receptors, adrenergic, alpha • blood pressure • catecholamines • signal transduction

This article has been cited by other articles:

				G. Asemu, N. S. Dhalla, and P. S. Tappia Inhibition of PLC improves postischemic recovery in isolated rat heart Am J Physiol Heart Circ Physiol, December 1, 2004; 287(6): H2598 - H2605. [Abstract] [Full Text] [PDF]

				Y. P. R. Jarajapu, F. Johnston, C. Berry, A. Renwick, J. C. McGrath, A. MacDonald, and C. Hillier Functional Characterization of alpha 1-Adrenoceptor Subtypes in Human Subcutaneous Resistance Arteries J. Pharmacol. Exp. Ther., November 1, 2001; 299(2): 729 - 734. [Abstract] [Full Text] [PDF]

				R. E. Shapiro, B. Winters, M. Hales, T. Barnett, D. A. Schwinn, N. Flavahan, and D. E. Berkowitz Endogenous Circulating Sympatholytic Factor in Orthostatic Intolerance Hypertension, October 1, 2000; 36(4): 553 - 560. [Abstract] [Full Text] [PDF]

				X. L. Rudner, D. E. Berkowitz, J. V. Booth, B. L. Funk, K. L. Cozart, E. B. D’Amico, H. El-Moalem, S. O. Page, C. D. Richardson, B. Winters, et al. Subtype Specific Regulation of Human Vascular {alpha}1-Adrenergic Receptors by Vessel Bed and Age Circulation, December 7, 1999; 100(23): 2336 - 2343. [Abstract] [Full Text] [PDF]