title: Insulin attenuates vasopressin-induced calcium transients and a voltage-dependent calcium response in rat vascular smooth muscle cells.
abstract: Insulin attenuates the contractile responses of vascular smooth muscle (VSM) to various agonists. Insulinopenic and insulin-resistant rats lack this normal attenuation of vascular contractile responses. To study this attenuating mechanism, the effects of insulin on calcium (Ca2+) responses of cultured VSM cells (a7r5) to arginine vasopressin (AVP) and membrane potential were investigated. Insulin (1 and 100 mU/ml) shifted AVP dose-response curves to the right, reducing relative potency of AVP by 16-fold and 220-fold, respectively. Responses to AVP were significantly attenuated within 30 min of insulin application. The AVP-elicited rise in [Ca2+]i was partially dependent upon extracellular Ca2+. AVP-elicited inward current was reduced by 90 min of insulin treatment (100 mU/ml), from a peak current of -103 +/- 27 pA (normal) to -37 +/- 15 pA (insulin treated). Peak voltage-dependent Ca(2+)-dependent inward current was unaffected by insulin; however, the current-voltage curve was shifted 16 +/-3 mV to the right by insulin. Thus, insulin may reduce VSM contractile responses by attenuating agonist-mediated rises in [Ca2+]i mediated, in part, by reductions in Ca2+ influx through both receptor- and voltage-operated channels.
authors.affiliation: Department of Physiology, Wayne State University, Detroit, Michigan 48201.
authors.forename: P R
authors.initials: PR
authors.lastname: Standley
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: J L
authors.initials: JL
authors.lastname: Ram
authors.forename: M B
authors.initials: MB
authors.lastname: Zemel
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
mesh_terms: D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects*; D002478:Cells, Cultured; D048909:Diabetes Complications; D006973:Hypertension / Q000209:etiology; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats
chemical_list: D015220:Calcium Channels; D007328:Insulin; D001127:Arginine Vasopressin; D002118:Calcium