Abstract
Alpha1-adrenoceptors were identified in murine tissues by [3H]prazosin saturation binding studies, with a rank order of cerebral cortex > cerebellum > liver > lung > kidney > heart > spleen, with the spleen not exhibiting detectable expression. Competition binding studies were performed with 5-methylurapidil, BMY 7378, methoxamine, (+)-niguldipine, noradrenaline, SB 216469 and tamsulosin. On the basis of monophasic low-affinity competition by BMY 7378,alpha1D-adrenoceptors were not detected at the protein level in any tissue. On the basis of competition studies with thealpha1A/alpha1B-discriminating drugs, alpha1B-adrenoceptors appeared to be the predominant or even the sole subtype in murine liver, lung and cerebellum, whereas murine cerebral cortex and kidney contained ∼30% and 50% of alpha1A-adrenoceptors, respectively. The affinities of the various competitors in the murine tissues were quite similar to those reported from other species. The ratio of high- and low-affinity sites for tamsulosin did not in all cases match the percentages of alpha1A- andalpha1B-adrenoceptors detected by the other competitors; however, the low-affinity component of the tamsulosin competition curves was abolished in the cerebral cortex ofalpha1B-adrenoceptor knockout mice. Treatment with chloroethylclonidine (10 μM, 30 min, 37°C) inactivated the alpha1-adrenoceptors in all tissues by >75%. When the concentration-dependent inactivation of tissue alpha1B-adrenoceptors (liver) and tissue alpha1A-adrenoceptors (cerebral cortex from alpha1B-adrenoceptor knockout mice) was compared, alpha1A-adrenoceptors were only slightly less sensitive toward chloroethylclonidine thanalpha1B-adrenoceptors. We conclude that murine tissues express alpha1A- andalpha1B-adrenoceptors, which are largely similar to those in other species. However, the tissue-specific distribution of subtypes may differ from that of other species.
Footnotes
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Send reprint requests to: Dr. Martin C. Michel, Nephrology Laboratory IG 1, Klinikum, 45122 Essen, Germany. E-mailmartin.michel{at}uni-essen.de
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↵1 This work was supported in part by grants from the Deutsche Forschungsgemeinschaft and Fonds National Suisse de la Recherche Scientifique (3100–051043).
- Abbreviations:
- BMY 7378
- (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride)
- SB 216469
- N-(3-[4-(2-methoxyphenyl)-l-piperazinyl]propyl)-3-methyl)-4-oxo-2-phenyl-4H-l-benzopyran-8-carboxamide monomethanesulfonate monohydrate
- IC50
- median inhibitory concentration
- Received November 10, 1997.
- Accepted April 29, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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