Effects of pinaverium on voltage-activated calcium channel currents of single smooth muscle cells isolated from the longitudinal muscle of the rabbit jejunum.
1. Smooth muscle cells of the longitudinal muscle of the rabbit jejunum were dispersed by enzyme treatment and recordings of membrane current were made in the whole-cell mode by patch clamp technique. The action of pinaverium bromide on the voltage-dependent inward current of single isolated smooth muscle cells was studied in solutions containing normal concentrations of calcium or high concentrations of barium at room temperature. 2. Pinaverium reduced the voltage-dependent inward current with an IC50 of 1.5 microM. This IC50 is similar to those of verapamil, diltiazem and flunarizine on these cells as described by others. Occasionally evidence of a potentiating action of pinaverium on the inward current was seen. 3. Repetitive stimulation of the cells did not increase blockade of inward current by pinaverium unlike the use-dependent blockade seen with verapamil, methoxyverapamil, and diltiazem in these and in other smooth muscle cells. 4. The inactivation of inward current was studied by holding at various potentials for 2 or 10 s before evoking inward current. The voltage at which current was 50% available was changed very little by pinaverium although other calcium entry blockers, for example the dihydropyridines, have been reported to produce appreciable negative shifts which indicate considerable voltage-dependence of their blockade. This may indicate that pinaverium has similar affinities for the closed available and inactivated calcium channel states so that blockade is not appreciably voltage-dependent.
Beech
D J
DJ
Department of Pharmacology, St George's Hospital Medical School, London, U.K.
MacKenzie
I
I
Bolton
T B
TB
Christen
M O
MO
D000818:Animals; D001464:Barium / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D004110:Diltiazem / Q000494:pharmacology; D005444:Flunarizine / Q000494:pharmacology; D005711:Gallopamil / Q000494:pharmacology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D007583:Jejunum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010276:Parasympatholytics / Q000494:pharmacology*; D011817:Rabbits; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D007473:Ion Channels; D009025:Morpholines; D010276:Parasympatholytics; D001464:Barium; D005711:Gallopamil; D014700:Verapamil; D004110:Diltiazem; D005444:Flunarizine; C013199:pinaverium