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KMID : 0811720230270040325
Korean Journal of Physiology & Pharmacology
2023 Volume.27 No. 4 p.325 ~ p.331
Involvement of ¥á1B-adrenoceptors and Rho kinase in contractions of rat aorta and mouse spleen
Hadeel A. Alsufyani

James R. Docherty
Abstract
¥á1-adrenoceptors link via the G-protein Gq/G11 to both Ca2+ entry and release from stores, but may also activate Rho kinase, which causes calcium sensitization. This study aimed to identify the subtype(s) of ¥á1-adrenoceptor involved in Rho kinase-mediated responses in both rat aorta and mouse spleen, tissues in which contractions involve multiple subtypes of ¥á1-adrenoceptor. Tissues were contracted with cumulative concentrations of noradrenaline (NA) in 0.5 log unit increments, before and in the presence of an antagonist or vehicle. Contractions produced by NA in rat aorta are entirely ¥á1-adrenoceptor mediated as they are competitively blocked by prazosin. The ¥á1A-adrenoceptor antagonist RS100329 had low potency in rat aorta. The ¥á1D-adrenoceptor antagonist BMY7378 antagonized contractions in rat aorta in a biphasic manner: low concentrations blocking ¥á1D-adrenoceptors and high concentrations blocking ¥á1B-adrenoceptors. The Rho kinase inhibitor fasudil (10 ¥ìM) significantly reduced aortic contractions in terms of maximum response, suggesting inhibition of ¥á1B-adrenoceptor mediated responses. In the mouse spleen, a tissue in which all 3 subtypes of ¥á1-adrenoceptor are involved in contractions to NA, fasudil (3 ¥ìM) significantly reduced both early and late components to the NA contraction, the early component involving ¥á1B- and ¥á1D-adrenoceptors, and the late component involving ¥á1B- and ¥á1A-adrenoceptors. This suggests that fasudil inhibits ¥á1B-adrenoceptor mediated responses. It is concluded that ¥á1D- and ¥á1B-adrenoceptors interact in rat aorta and ¥á1D-, ¥á1A- and ¥á1B-adrenoceptors interact in the mouse spleen to produce contractions and these interactions suggest that one of the receptors preferentially activates Rho kinase, most likely the ¥á1B-adrenoceptor.
KEYWORD
¥á1B-adrenoceptors, ¥á1D-adrenoceptors, BMY7378, Fasudil, Rho kinase
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