EFFECT OF CROMAKALIM AND GLIBENCLAMIDE ON SPONTANEOUS AND EVOKED MOTILITY OF THE GUINEA-PIG ISOLATED RENAL PELVIS AND URETER

Citation
Ca. Maggi et al., EFFECT OF CROMAKALIM AND GLIBENCLAMIDE ON SPONTANEOUS AND EVOKED MOTILITY OF THE GUINEA-PIG ISOLATED RENAL PELVIS AND URETER, British Journal of Pharmacology, 111(3), 1994, pp. 687-694
Citations number
35
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00071188
Volume
111
Issue
3
Year of publication
1994
Pages
687 - 694
Database
ISI
SICI code
0007-1188(1994)111:3<687:EOCAGO>2.0.ZU;2-G
Abstract
1 We have investigated the effect of the potassium (K) channel opener, cromakalim, on the spontaneous myogenic activity of the guinea-pig is olated renal pelvis and on myogenic contractions evoked by direct elec trical stimulation of, the guinea-pig isolated ureter. 2 In the presen ce of Bay K 8644 (1 mu M), electrical stimulation of the guinea-pig ur eter (10 Hz for 1 s, pulse width 5 ms, 60 V) produced regular tetrodot oxin-(1 mu M) resistant phasic contractions which were suppressed by 3 mu M cromakalim. Glibenclamide (0.1-3 mu M), 4-aminopyridine (4-AP, 0 .1-2 mM) and tetraethylammonium (TEA, 1-10 mM) produced a concentratio n-dependent inhibition of the effect of cromakalim with the rank order of potency (EC(50) in parentheses): glibenclamide (0.64 mu M)> >4.AP (1.11 mM) > TEA (6.6 mM), Apamin (0.1-0.3 mu M) was without effect. 3 Cromakalim (0.1-10 mu M) produced concentration-dependent inhibition a nd suppression of spontaneous contractions of the guinea-pig isolated renal pelvis and of evoked contractions of the ureter with ECS, values of 0.71 and 0.47 mu M, respectively. 4 Glibenclamide (1 mu M) produce d a rightward shift of the concentration-response curve to cromakalim in both the renal pelvis and ureter, without producing depression of t he maximal inhibitory effect. Glibenclamide did not affect the spontan eous activity of the renal pelvis while it produced a slight enhanceme nt (10-15% increase) of evoked contractions of the ureter. Glibenclami de did not affect the inhibitory action of the adenylate cylase activa tor, forskolin, in the renal pelvis or ureter. 5 In electrophysiologic al experiments (sucrose gap), cromakalim (0.3 and 1 mu m) produced hyp erpolarization of ureter smooth muscle. Cromakalim also produced a tra nsient suppression of action potentials and accompanying phasic contra ctions evoked by electrical stimulation. Before suppression of evoked contractions, a shortening of action potential duration was observed c oncomitant with the developing hyperpolarization produced by cromakali m. A lower concentration (0.1 mu M) of cromakalim did not affect membr ane potential but shortened action potential duration and reduced the evoked contraction. 6 Glibenclamide (1 mu M) inhibited the hyperpolari zing action of cromakalim and prevented its inhibitory action on evoke d action potentials and contractions of the ureter. Glibenclamide also produced a slight prolongation of action potential duration and incre ased the amplitude and duration of the accompanying mechanical respons e. 7 These findings demonstrate that activation of cromakalim- and gli benclamide-sensitive K channels produces a powerful mechanism for regu lation of pyeloureteral motility and suppression of latent pacemakers of the ureter in guinea-pig. Glibenclamide-sensitive K channels take p art in determining action potential shape and duration in the guinea-p ig ureter.