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

Abstract

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.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 IC 50 values in human colonic circular muscle were ∼100 and 31.0 μM, 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 × 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(O tBu). 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.