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 was studied in isolated guinea-pig taenia coli and human colonic circular muscle, using identical field stimulation parameters (rectangular pulses of 0.5 ms duration, 9 V x cm(-1) intensity, trains of 3 pulses at 0.5 Hz, repeated every 1/3/5 min). The stimulation-induced contractions were inhibited in both preparations by GABA and baclofen; the IC50 values in human colonic circular muscle were approximately 100 and 31.0 microM, 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 colonic circular muscle, inhibition by 3 x 10(-5) M baclofen was fully reversed by 10(-3) M CGP 35348. With the exception of caecum, the delta 2 opioid receptor agonist deltorphin II was a potent inhibitor in human colonic circular muscle. 10(-8) M Deltorphin caused a 74.4 +/- 9.6% (n = 4) inhibition which was reversed by 10(-6) M of delta receptor selective peptide antagonist BOC-Tyr-Pro-Gly-Phe-Leu-Thr(OtBu). 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 circular 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.