Saha J K, Sengupta J N, Goyal R K
Harvard Digestive Diseases Center, Charles A. Dana Research Institute, Boston, Massachusetts.
J Pharmacol Exp Ther. 1990 Mar;252(3):1012-20.
Bradykinin (BK) produced a concentration-dependent contraction of the longitudinal but not the circular muscle of the opossum esophagus. The pD2 value of BK on the longitudinal muscle was 6.58 +/- 0.06 M. The maximal response of the longitudinal muscle to BK was 44% compared to carbachol. The putative B1 agonist des-Arg9-BK produced contraction of longitudinal muscle but the putative B1 receptor antagonist des-Arg9-[Leu8]-BK (20 and 50 microM) did not modify the responses to BK or des-Arg9-BK. The putative B2 antagonists d-Phe7-BK, Thi5,8-d-Phe7-BK and d-Arg0-Hyp3-Thi5,8-d-Phe7-BK (B6572) were found to be agonists in this tissue. The rank order of potency with respect to Emax obtained from cumulative concentration-response curves was BK greater than Thi5,8-d-Phe7-BK greater than B6572 greater than d-Phe7-BK and pD2 values of these compounds were 6.58 +/- 0.06, 6.30 +/- 0.28, 6.74 +/- 0.08 and 5.05 +/- 0.04 M, respectively. The excitatory effect of BK and Thi5,8-d-Phe7-BK was not modified by tetrodotoxin (1 and 10 microM), atropine (1 microM) or indomethacin (1 and 10 microM), but was significantly (P less than .001) inhibited by nifedipine (1 and 10 microM). Three putative "tissue selective" BK antagonists, d-Phe2,7-BK (B4404), d-Phe7-Hyp8-BK and Phe2-d-Phe7-BK also had an agonistic effect on longitudinal muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
