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

We have tested the effect of the gap junction inhibitor, 18β‐glycyrrhetinic acid (18βGA) on electromechanical coupling in the guinea‐pig renal pelvis and ureter by the sucrose gap technique. In the ureter 18βGA (3–30 μM) 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. 18βGA (30 μM) markedly inhibited the depolarization and APs evoked by NKA. However the contractile response was more sustained in the presence than in the absence of 18βGA. At 100 μ M , 18βGA inhibited the mechanical responses to NKA. KCl (80 mM) produced APs and phasic contractions followed by sustained depolarization and tonic contraction. At 30 μ M 18βGA markedly inhibited the KCl‐evoked APs and phasic contractions without affecting the sustained responses. At 100 μ M 18βGA inhibited the tonic contraction to KCl. In the renal pelvis 18βGA (30 μM) 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 μM, the action of 18βGA 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 18βGA 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; doi: 10.1038/sj.bjp.0703004