Different atypical beta-adrenoceptors mediate isoprenaline-induced relaxation in vascular and non-vascular smooth muscles.

Atypical beta-adrenoceptors mediating smooth muscle relaxation were compared in several rat tissues including the distal colon, fundic strip, thoracic aorta and common carotid artery. Isoprenaline, CGP 12177 and BRL 37344 concentration-dependently relaxed longitudinal strips of the distal colon and fundus precontracted with carbachol (10(-6)M) as well as ring segments of the aorta and carotid artery precontracted with noradrenaline (10(-7)M). The rank order of potency was isoprenaline = BRL 37344 > CGP 12177 in the distal colon, isoprenaline = CGP 12177 > BRL 37344 in the aorta and carotid artery segments and isoprenaline > BRL 37344 > CGP 12177 in the fundic strip. Pretreatment with BRL 37344 induced a marked desensitization of the distal colon and fundic strips but not the aorta and carotid artery to isoprenaline. In the fundus and distal colon, pretreatment with CGP 12177 (10(-4)M abolished the effect of isoprenaline. Cyanopindolol (10(-6)M) shifted the isoprenaline curve to the right, without reducing the maximum response, in the distal colon fundic strip. -logKB values were 7.44 +/- 0.08 and 7.53 +/- 0.10 in the distal colon and fundic strip respectively. The same concentration of cyanopindolol did not inhibit the relaxant effect of isoprenaline in the aorta and carotid artery segments. It was therefore concluded that atypical beta-adrenoceptors in these preparations were not identical, indicating heterogeneity of atypical beta-adrenoceptors.