MURINE ALPHA(1)-ADRENOCEPTOR SUBTYPES - I - RADIOLIGAND BINDING-STUDIES

Alpha(1)-adrenoceptors were identified in murine tissues by [H-3]prazo sin 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, (+)-niguldipi ne, noradrenaline, SE 216469 and tamsulosin. On the basis of monophasi c low-affinity competition by BMY 7378, alpha(1D)-adrenoceptors were n ot detected at the protein level in any tissue. On the basis of compet ition studies with the alpha(1A)/alpha(1B)-discriminating drugs, alpha (1B)-adrenoceptors appeared to be the predominant or even the sole sub type in murine liver, lung and cerebellum, whereas murine cerebral cor tex and kidney contained similar to 30% and 50% of alpha(1A)-adrenocep tors, respectively. The affinities of the various competitors in the m urine tissues were quite similar to those reported from other species. The ratio of high- and low-affinity sites for tamsulosin did not in a ll cases match the percentages of alpha(1A)- and alpha(1B)-adrenocepto rs detected by the other competitors; however, the low-affinity compon ent of the tamsulosin competition curves was abolished in the cerebral cortex of alpha(1B)-adrenoceptor knockout mice. Treatment with chloro ethylclonidine (10 mu M, 30 min, 37 degrees C) inactivated the alpha(1 )-adrenoceptors in all tissues by >75%. When the concentration-depende nt inactivation of tissue alpha(1B)-adrenoceptors (liver) and tissue a lpha(1A)-adrenoceptors (cerebral cortex from alpha(1B)-adrenoceptor kn ockout mice) was compared, alpha(1A)-adrenoceptors were only slightly less sensitive toward chloroethylclonidine than alpha(1B)-adrenoceptor s. We conclude that murine tissues express alpha,, and alpha(1B)-adren oceptors, which are largely similar to those in other species. However , the tissue-specific distribution of subtypes may differ from that of other species.