Modulation by GABA(B) and delta opioid receptors of neurally induced responses in isolated guinea-pig taenia coli and human colonic circular muscle

The GABA-ergic and opioid modulation of neurally induced muscle responses w as studied in isolated guinea-pig taenia coli and human colonic circular mu scle, using identical field stimulation parameters (rectangular pulses of 0 .5 ms duration, 9 V.cm(-1) intensity, trains of 3 pulses at 0.5 Hz, repeate d every 1/3/5 min).The stimulation-induced contractions were inhibited in b oth preparations by GABA and baclofen; the IC50 values in human colonic cir cular muscle were similar to 100 and 31.0 mu M, respectively. In guinea-pig taenia coli, the inhibition by 10(-4) M GABA was dose-dependently reversed by 10(-4)-10(-3) M of GABA(B) receptor antagonist CGP 35348; antagonism by phaclofen was less effective in the same concentration range. In human col onic circular muscle, inhibition by 3 x 10(-5) M baclofen was fully reverse d by 10(-3) M CGP 35348. With the exception of caecum, the delta 2 opioid r eceptor agonist deltorphin Il was a potent inhibitor in human colonic circu lar muscle. 10(-8) M Deltorphin caused a 74.4 +/- 9.6% (n = 4) inhibition w hich was reversed by 10(-6) M of delta receptor selective peptide antagonis t BOC-Tyr-Pro-Gly-Phe-Leu-Thr((OBu)-Bu-t). Deltorphin II was ineffective in guinea-pig taenia coli even at 10(-6) M; the same concentration caused an 84.3 +/- 7.9 (n = 4) inhibition in human preparations. It is concluded that : 1) GABA-ergic modulatory mechanisms are present both in human colonic cir cular muscle and guinea-pig taenia coli; 2) the GABA receptors involved are of type B; and 3) delta opioid receptor-mediated modulation functions only in human colonic circular muscle in regions other than the caecum. (C) 200 0 Elsevier Science Ltd. Published by Editions scientifiques et medicales El sevier SAS.