Interaction between α 1B ‐ and other α 1 ‐ and α 2 ‐adrenoceptors in producing contractions of mouse spleen

Alsufyani, H. A., Daly, C. and Docherty, J. R. (2021) Interaction between α 1B ‐ and other α 1 ‐ and α 2 ‐adrenoceptors in producing contractions of mouse spleen. Basic and Clinical Pharmacology and Toxicology, 129(6), pp. 416-426. (doi: 10.1111/bcpt.13639) (PMID:34383990)

Abstract

We have investigated the interaction of α1- and α2-adrenoceptor subtypes in producing isometric contractions to NA in mouse whole spleen. The α1-adrenoceptor antagonist prazosin (10-8M) or the α2-adrenoceptor antagonist yohimbine (10-6M) alone produced only small shifts in NA potency in wild type (WT) mice, but the combination produced a large shift in NA potency. In spleen from α1A/D-KO mice, the effects of prazosin and the combination of prazosin and yohimbine were similar to their effects in WT mice. Hence, in α1A/D-KO mice, in which the only α1-adrenoceptor present is the α1B-adrenoceptor, prazosin still antagonized contractions to NA. The α1A-adrenoceptor antagonist RS100329 (3x10-9M) produced significant shifts in the effects of higher concentrations of NA (EC50 and EC75 levels) and the α1D-adrenoceptor antagonist BMY7378 (3x10-8M) produced significant shifts in the effects of lower concentrations of NA (EC25 and EC50 levels). The effects of BMY7378 and RS00329 demonstrate α1D-adrenoceptor and α1A-adrenoceptor components, and suggest that the α1B-adrenoceptor interacts with an α1D-adrenoceptor, and to a lesser extent an α1A-adrenoceptor, at low, and an α1A-adrenoceptor at high, NA concentrations. This study demonstrates the complex interaction between α1- and α2-adrenoceptor subtypes in producing contractions of mouse spleen and may have general implications for α-adrenoceptor mediated control of smooth muscle.

• Item Type: Articles
• Additional Information: This project was part funded by the Deanship of Scientific Research, King Abdulaziz University, Jeddah, grant no. J:12-248-1440 (HAA).
• Keywords: Toxicology, pharmacology, general medicine.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Daly, Professor Craig
• Authors: Alsufyani, H. A., Daly, C., and Docherty, J. R.
• College/School: College of Medical Veterinary and Life Sciences > School of Life Sciences
• Journal Name: Basic and Clinical Pharmacology and Toxicology
• Publisher: Wiley
• ISSN: 1742-7835
• ISSN (Online): 1742-7843
• Published Online: 25 September 2021
• Copyright Holders: Copyright © 2021 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society)
• First Published: First published in Basic and Clinical Pharmacology and Toxicology 129(6): 416-426
• Publisher Policy: Reproduced in accordance with the publisher copyright policy