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.
Makó
E
E
Department of Pharmacology, Semmelweis University of Medicine, Budapest, Hungary.
Rónai
A Z
AZ
Adám
G
G
Juhász
G
G
Ritter
L
L
Lestár
B
B
Crunelli
V
V
D000328:Adult; D000368:Aged; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D005260:Female; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000294:innervation; D009842:Oligopeptides / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018080:Receptors, GABA-B / Q000187:drug effects*; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009842:Oligopeptides; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; D017465:Receptors, Opioid, delta; C052329:phaclofen; C060209:deltorphin II, Ala(2)-; C103096:tert-butyloxycarbonyl-tyrosyl-prolyl-glycyl-phenylalanyl-leucyl-(O-tert-butyl)threonine; C066430:CGP 35348; D001418:Baclofen