title: Calcium influx and protein kinase C activation involved in uterine vasoconstriction in guinea pigs.
abstract: The mechanical responses of circular segments of uterine arteries to different combinations of vasoactive agents and putative inhibitors of calcium fluxes were examined using a sensitive in vitro method. Exposure to high potassium (127 mM) or to noradrenaline (NA; 0.1 mM) resulted in a rapid, initial increase in tension of the vascular preparation to reach a sustained level of contraction (approximatively 12 mN) which lasted for at least 15 min. The protein kinase C activator, 4-beta-phorbol-12,13-esther-dibutyrate (10 microM), induced a slowly developing but sustained contractile response with a maximum (PDBumax) of only 4 mN. Addition of the calcium ionophore, A23187, to PDBu-contracted vessels did not increase tension, while the maximum tension evoked by A23187 per se (3 microM) was 5 mN. Ionomycin had only a small contractile effect on the uterine artery. The contraction evoked by depolarization (potassium) or alpha 1-adrenoceptor stimulation (NA) was decreased in nominally calcium-free medium containing EDTA (0-100 microM) or EGTA, while uterine arteries loaded intracellularly with the calcium chelator, quin-2, responded to the vasoconstrictors almost as well as the control preparations. Blockade of calcium influx with Cd2+ (greater than 0.01 mM), nifedipine (greater than 3 microM), verapamil (greater than 1 microM) and TMB-8 (greater than 10 microM) reduced the tension evoked by potassium somewhat more than it reduced the contractions induced by NA, while the opposite was seen in the presence of Ni2+ (greater than 0.1 mM). Inhibition of calmodulin-dependent enzymes by W7 (greater than 10 microM) reduced the maximum tension evoked by potassium and NA to a similar extent.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Zoophysiology, University of Lund, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Fallgren
authors.forename: H
authors.initials: H
authors.lastname: Bergstrand
authors.forename: L
authors.initials: L
authors.lastname: Edvinsson
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects; D014599:Uterus / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D002121:Calcium Channel Blockers; D011493:Protein Kinase C; D002118:Calcium; D009638:Norepinephrine