Effect of 18β-glycyrrhetinic acid on electromechanical coupling in the guinea-pig renal pelvis and ureter

1 We have tested the effect of the gap junction inhibitor, 18 beta-glycyrrhetinic acid (18 beta GA) on electromechanical coupling in the guinea-pig renal pelvis and ureter by the sucrose gap technique. 2 In the ureter 18 beta GA (3-30 mu M) produced a concentration-dependent inhibition of the spike component of the action potential (AP) and reduced contraction evoked by electrical stimulation. 3 Neurokinin A (NKA) produced a slow depolarization with superimposed APs and phasic contractions of the ureter. 18 beta GA (30 mu M) markedly inhibited the depolarization and APs evoked by NKA. However the contractile response was more sustained in the presence than in the absence of 18 beta GA. At 100 mu M, 18 beta GA inhibited the mechanical responses to NKA. 4 KCl (80 mM) produced APs and phasic contractions followed by sustained depolarization and tonic contraction. At 30 mu M 18 beta GA markedly inhibited the KCl-evoked APs and phasic contractions without affecting the sustained responses. At 100 mu M 18 beta GA inhibited the tonic contraction to KCl. 5 In the renal pelvis 18 beta GA (30 mu M) inhibited the amplitude of pacemaker potentials and accompanying contractions and induced the appearance of low-amplitude APs not associated with contraction. 6 We conclude that, up to 30 mu M, the action of 18 beta GA is consistent with an inhibition of cell-to-cell electrical coupling via gap junctions. The single-unit character of smooth muscles in the guineapig upper urinary tract is partly converted to a multi-unit pattern. At high concentrations 18 beta CA possesses non specific effects which limit its usefulness as a tool for studying the role of gap junctions in smooth muscles.