Contraction of human colonic circular smooth muscle cells is inhibited by the calcium channel blocker pinaverium bromide.
The effects of L-type calcium channel blockers (CCBs) selective for the gastrointestinal tract (pinaverium) or non-selective (nicardipine and diltiazem), were investigated on CCK-, CCh- or KCl-induced contraction of smooth muscle cells (SMC) isolated from the circular muscle layer of normal or of inflamed human colons. In the normal tissue colon, whatever the contractile agent used, CCK-8 (1nM), CCh (1nM) or KCl (20mM), a micromolar concentration of pinaverium significantly inhibited contraction (88.36%, 93.10%, 93.92% inhibition respectively); this effect was concentration-dependent for CCh (IC50 = 0.73 +/- 0.08nM) and for CCK (IC50 = 0.92 +/- 0.12nM). In parallel, both nicardipine and diltiazem inhibit significantly contraction of isolated SMC. In inflamed colons, pinaverium (1 microM) display a significant higher efficacy than diltiazem or nicardipine to reduce cell contraction induced by CCK-8 or by KCl. In addition, RT-PCR experiments were performed to evidence tissue specificity of the L-type calcium channel. They revealed the expression of the messenger of the a-1 subunit L-type calcium channel (binding site of such CCBs), consistent with the expression of the rbC-2 splice variant of the alpha1-C gene.


CONCLUSIONS
(i) the inhibition by calcium channel blockers of agonist-induced contractile activity suggest a modulation of SMC contraction upon extracellular calcium via 'L-type' voltage-dependent calcium channel; (ii) this study provides a rationale for the clinical use of pinaverium in colonic motor disoders affecting the contractility of SMC, since it appeared to decrease the contraction even in pathological situation; and (iii) RT-PCR experiments confirms the presence in human colon SMC of the alpha-1 subunit mRNA of calcium channel.
Boyer
J C
JC
Unité Fonctionnelle d'Exploration de la Fibre Musculaire Lisse, CHU Carémeau, Nimes, France.
Magous
R
R
Christen
M O
MO
Balmes
J L
JL
Bali
J P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001665:Binding Sites / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D003092:Colitis / Q000503:physiopathology*; D003106:Colon / Q000166:cytology / Q000502:physiology; D004110:Diltiazem / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009025:Morpholines / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D009529:Nicardipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000302:isolation & purification; D012844:Sincalide / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009025:Morpholines; D021122:Protein Subunits; D012333:RNA, Messenger; D011189:Potassium Chloride; D009529:Nicardipine; D004110:Diltiazem; D012844:Sincalide; C013199:pinaverium