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Beta-adrenoceptor mechanisms were studied in the isolated guinea-pig taenia caecum. Isoprenaline, desisopropylprocaterol and carteolol relaxed guinea-pig taenia caecum, and their intrinsic activities (mean +/- S.E.) were 1.0, 0.95 +/- 0.03 and 0.61 +/- 0.08, respectively. The pD2 values (mean +/- S.E.) were 8.59 +/- 0.06 for isoprenaline, 7.94 +/- 0.21 for desisopropylprocaterol and 6.35 +/- 0.14 for carteolol. The beta-adrenoceptors in guinea-pig taenia caecum were irreversibly inactivated by photoaffinity labeling with isoprenaline (6 X 10(-6) M). Photoinactivation of beta-adrenoceptors caused a considerable parallel shift in the dose-response curve of isoprenaline. The decline of the dose-response curves of desisopropylprocaterol and carteolol without a preceding shift was observed after photoinactivation. Isoprenaline, desisopropylprocaterol and carteolol increased cyclic AMP levels in guinea-pig taenia caecum, and the pD2 values were 7.43, 6.97 and 5.96, respectively. When differences between the pD2 values for test drugs obtained from the mechanical responses and from the increases of cyclic AMP levels were calculated, the differences for isoprenaline was larger than those for desisopropylprocaterol and carteolol. The dose-response curves for relaxation and cyclic AMP level by isoprenaline were both shifted to the right as a result of prior incubation with carteolol. These results suggest that there are spare receptors for isoprenaline, but few for desisopropylprocaterol and carteolol in the smooth muscle.

Relationship between intrinsic activity of .BETA.-adrenoceptor agonist and amount of spare receptors in guinea pig taenia caecum.