Effect of 18beta-glycyrrhetinic acid on electromechanical coupling in the guinea-pig renal pelvis and ureter.
We have tested the effect of the gap junction inhibitor, 18beta-glycyrrhetinic acid (18betaGA) on electromechanical coupling in the guinea-pig renal pelvis and ureter by the sucrose gap technique. In the ureter 18betaGA (3 - 30 microM) produced a concentration-dependent inhibition of the spike component of the action potential (AP) and reduced contraction evoked by electrical stimulation. Neurokinin A (NKA) produced a slow depolarization with superimposed APs and phasic contractions of the ureter. 18betaGA (30 microM) markedly inhibited the depolarization and APs evoked by NKA. However the contractile response was more sustained in the presence than in the absence of 18betaGA. At 100 microM, 18betaGA inhibited the mechanical responses to NKA. KCl (80 mM) produced APs and phasic contractions followed by sustained depolarization and tonic contraction. At 30 microM 18betaGA markedly inhibited the KCl-evoked APs and phasic contractions without affecting the sustained responses. At 100 microM 18betaGA inhibited the tonic contraction to KCl. In the renal pelvis 18betaGA (30 microM) inhibited the amplitude of pacemaker potentials and accompanying contractions and induced the appearance of low-amplitude APs not associated with contraction. We conclude that, up to 30 microM, the action of 18betaGA is consistent with an inhibition of cell-to-cell electrical coupling via gap junctions. The single-unit character of smooth muscles in the guinea-pig upper urinary tract is partly converted to a multi-unit pattern. At high concentrations 18betaGA possesses non specific effects which limit its usefulness as a tool for studying the role of gap junctions in smooth muscles. British Journal of Pharmacology (2000) 129, 163 - 169
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Pharmacology Department, Menarini Ricerche s.p.a., Via Rismondo 12A, 50131, Florence Italy.
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D004558:Electric Stimulation; D004594:Electrophysiology; D017629:Gap Junctions / Q000187:drug effects*; D006034:Glycyrrhetinic Acid / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007682:Kidney Pelvis / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D014513:Ureter / Q000187:drug effects* / Q000502:physiology
D015288:Neurokinin A; D006034:Glycyrrhetinic Acid