title: Effect of calmodulin antagonists on contraction and 45Ca movements in rat aorta.
abstract: To study the selectivity of calmodulin antagonists it was assumed that they should inhibit noradrenaline (NA)- and K(+)-induced contractions similarly without an accompanying inhibition of 45Ca uptake. Therefore, in isolated rat aorta the effects of W-7, calmidazolium and trifluoperazine on contraction and 45Ca uptake elicited by K+ and NA were investigated. Calmidazolium (10(-5)-10(-4) mol/l) elicited an incomplete inhibiton of K(+)- and NA-induced contraction and 45Ca uptake. Trifluoperazine inhibited the NA-induced contractions at lower concentrations (10(-8)-10(-6) mol/l) than the K(+)-induced contraction (10(-6)-10(-4) mol/l). The K(+)- and NA-induced 45Ca uptake was blocked by trifluoperazine (10(-5) mol/l). W-7 (10(-5)-10(-4) mol/l) inhibited the K(+)- and NA-induced contraction, however, in the same concentration range W-7 diminished the K(+)- and NA-induced 45Ca uptake. In conclusion, the results indicate that calmidazolium and trifluoperazine are hardly useful as calmodulin antagonists because of their additional properties, whereas W-7 seems to be the least unspecific of the calmodulin antagonists studies.
authors.affiliation: Janssen Research Foundation, Neuss, FRG.
authors.forename: D
authors.initials: D
authors.lastname: Wermelskirchen
authors.forename: P
authors.initials: P
authors.lastname: Koch
authors.forename: D
authors.initials: D
authors.lastname: Wilhelm
authors.forename: U
authors.initials: U
authors.lastname: Nebel
authors.forename: A
authors.initials: A
authors.lastname: Leidig
authors.forename: B
authors.initials: B
authors.lastname: Wilffert
authors.forename: T
authors.initials: T
authors.lastname: Peters
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000494:pharmacology; D014268:Trifluoperazine / Q000494:pharmacology
chemical_list: D002132:Calcium Radioisotopes; D002147:Calmodulin; D007093:Imidazoles; D013449:Sulfonamides; D014268:Trifluoperazine; C031938:calmidazolium; C017967:W 7; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine