title: Potential L-Type Voltage-Operated Calcium Channel Blocking Effect of Drotaverine on Functional Models.
abstract: Drotaverine is considered an inhibitor of cyclic-3',5'-nucleotide-phophodiesterase (PDE) enzymes; however, published receptor binding data also support the potential L-type voltage- operated calcium channel (L-VOCC) blocking effect of drotaverine. Hence, in this work, we focus on the potential L-VOCC blocking effect of drotaverine by using L-VOCC-associated functional in vitro models. Accordingly, drotaverine and reference agents were tested on KCl-induced guinea pig tracheal contraction. Drotaverine, like the L-VOCC blockers nifedipine or diltiazem, inhibited the KCl-induced inward Ca2+- induced contraction in a concentration- dependent fashion. The PDE inhibitor theophylline had no effect on the KCl-evoked contractions, indicating its lack of inhibition on inward Ca2+flow. Drotaverine was also tested on the L-VOCC-mediated resting Ca2+refill model. In this model, the extracellular Ca2+enters the cells to replenish the emptied intracellular Ca2+stores. Drotaverine and L-VOCC blocker reference molecules inhibited Ca2+replenishment of Ca2+-depleted preparations detected by agonist-induced contractions in post-Ca2+replenishment Ca2+-free medium. Theophylline did not modify the Ca2+store replenishment after contraction. It seems that drotaverine, but not theophylline, inhibits inward Ca2+flux. The addition of CaCl2to Ca2+-free medium containing the agonist induced inward Ca2+flow and subsequent contraction of Ca2+-depleted tracheal preparations. Drotaverine, similar to the L-VOCC blockers, inhibited inward Ca2+flow and blunted the slope of CaCl2-induced contraction in agonist containing Ca2+-free medium with Ca2+-depleted tracheal preparations. These results show that drotaverine behaves like L-VOCC blockers but, unlike PDE inhibitors using L-VOCC associated in vitro experimental models.
authors.affiliation: LabMagister Training and Science Ltd. Budapest, Hungary (Z.P., E.G.M.), Horvath Csaba Laboratory of Bioseparation Sciences, MMKK, University of Debrecen, Debrecen, Hungary (Z.P., A.G.), MTA-PA Translational Glycomics Research Group, MUKKI, University of Pannonia, Veszprem, Hungary (A.G.).
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Patai
authors.affiliation: LabMagister Training and Science Ltd. Budapest, Hungary (Z.P., E.G.M.), Horvath Csaba Laboratory of Bioseparation Sciences, MMKK, University of Debrecen, Debrecen, Hungary (Z.P., A.G.), MTA-PA Translational Glycomics Research Group, MUKKI, University of Pannonia, Veszprem, Hungary (A.G.) guttman@mik.uni-pannon.hu.
authors.forename: András
authors.initials: A
authors.lastname: Guttman
authors.affiliation: LabMagister Training and Science Ltd. Budapest, Hungary (Z.P., E.G.M.), Horvath Csaba Laboratory of Bioseparation Sciences, MMKK, University of Debrecen, Debrecen, Hungary (Z.P., A.G.), MTA-PA Translational Glycomics Research Group, MUKKI, University of Pannonia, Veszprem, Hungary (A.G.).
authors.forename: Endre G
authors.initials: EG
authors.lastname: Mikus
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002122:Calcium Chloride / Q000494:pharmacology; D055724:Electrophysiological Phenomena / Q000187:drug effects; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D010208:Papaverine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism / Q000502:physiology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D011189:Potassium Chloride; C005317:drotaverin; D010208:Papaverine; D002122:Calcium Chloride; D002118:Calcium