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Articles in PresS, published online ahead of print March 19, 2002
Physiol Genomics, 10.1152/physiolgenomics.00065.2001
Submitted on August 7, 2001
Accepted on March 6, 2002
1b-adrenoceptors in mouse
1 Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom
* To whom correspondence should be addressed. E-mail: c.daly{at}bio.gla.ac.uk.
Pharmacological analysis alone has failed to clarify the role of the three 1-adrenoceptor subtypes in modulating vascular tone, due to a lack of sufficiently selective antagonists, particularly for the 1B-adrenoceptor, and the complexity when three receptor subtypes are potentially activated by the same agonist. We adopted a combined genetics/pharmacology strategy based on the 1B-adrenoceptor knockout mouse. The potency of 3 1-adrenoceptor antagonists versus phenylephrine was tested in aorta, carotid, mesenteric and caudal isolated arteries from knockout (KO) and wildtype (WT) mice. In the KO mouse the pharmacology became straightforward showing 1D- in two major conducting arteries (aorta and carotid) and 1A- in two distributing arteries (mesenteric and caudal). Combining antagonist pharmacology and genetics simplified analysis of 1 mediated vasoconstriction, demonstrating that 1D- & 1A- are the major subtypes involved in vasoconstriction, with a minor but definite contribution from 1B- in every vessel.
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