G-proteins are involved in contractile responses of isolated mesenteric resistance arteries to agonists.
We evaluated whether GTP-binding regulatory proteins (G-proteins) are involved in responses of resistance arterial smooth muscle to contractile agonists. We therefore pretreated isolated sympathectomized mesenteric resistance arteries of the rat with pertussis toxin (PTX) and recorded their contractile responses to aluminium fluoride, endothelin, high potassium, phenylephrine, phorbol myristate acetate, serotonin and vasopressin. PTX reduced contractile responses to agonists with the following order of potency: phenylephrine = serotonin greater than vasopressin = endothelin. The toxin reduced responses to phenylephrine in both the presence and absence of extracellular Ca2+. In Ca2(+)-depleted vessels that were exposed to phenylephrine, PTX virtually abolished responses to Ca2+ while hardly affecting responses to Ca2+ in the presence of endothelin. Also aluminium fluoride and phorbol myristate acetate induced contractions. These were dependent on extracellular Ca2+ and inhibited by felodipine. PTX reduced responses to aluminium fluoride but not those to phorbol myristate acetate. These data indicate that PTX sensitive G-proteins are involved in both influx of Ca2+ and release of intracellular Ca2+ following alpha 1-adrenergic and serotonergic stimulation of resistance arteries. The role of G-proteins in stimulated Ca2+ influx could involve a direct effect on calcium channels although an indirect effect through protein kinase-C can not be entirely excluded. The persistance of contractile responses to vasopressin and endothelin following PTX suggests that these agonists engage different pathways to induce contraction or have a higher efficacy in activating similar G-proteins.
Boonen
H C
HC
Department of Pharmacology, University of Limburg, Maastricht, The Netherlands.
De Mey
J G
JG
D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000818:Animals; D002118:Calcium / Q000502:physiology; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D009119:Muscle Contraction / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D010716:Phosphatidylinositols; D010566:Virulence Factors, Bordetella; D000535:Aluminum; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D005459:Fluorides; D002118:Calcium; C032311:aluminum fluoride