Functional importance of alpha adrenoceptor-mediated, D600-insensitive Ca++ entry in rabbit aorta.
Specific receptor-linked Ca++ entry (RLCa++E) was studied separately from Ca++ release and potential-dependent Ca++ entry (PDCa++E) in rabbit aorta after incubation in a Ca++-free solution containing ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid to bind trace levels of Ca++ and including methoxyverapamil (D600) (10(-5) M) to inhibit PDCa++E. Adding norepinephrine (NE) under these conditions resulted in a transient response which was attributed to Ca++ release from a limited cellular store. Subsequent addition of Ca++ results in a sustained contraction that was dependent upon the concentration of agonist and Ca++. This maintained response which by definition was insensitive to D600 was attributed to RLCa++E, was extensively relaxed or inhibited by nitroprusside or nitroglycerin and was partially relaxed by KCl or tetraethylammonium. Contractions due to RLCa++E alone equaled or exceeded the peak tension attained solely as a result of Ca++ release. At higher NE concentrations (greater than 10(-7) M), RLCa++E provided sufficient Ca++ to attain and sustain maximal levels of developed tension without requiring any additional Ca++ from either PDCa++E or Ca++ release. This high flux capacity of these receptor-linked Ca++ channels may partially account for the relative insensitivity of contractile responses to these higher concentrations of NE to D600. The relative contribution of PDCa++E to the elevation of myoplasmic Ca++ and concurrent sensitivity to D600 was increased at lower concentrations of NE because the degree of Ca++ release and RLCa++E were relatively small. Additionally, it appears that RLCA++E may be attenuated by concomitant membrane depolarization.
Hester
R K
RK
Department of Medical Pharmacology & Toxicology, College of Medicine, Texas A & M University, College Station.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001464:Barium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005711:Gallopamil / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D013324:Strontium / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D011942:Receptors, Adrenergic, alpha; D013757:Tetraethylammonium Compounds; D009599:Nitroprusside; D001464:Barium; D005711:Gallopamil; D004533:Egtazic Acid; D011189:Potassium Chloride; D006632:Histamine; D005996:Nitroglycerin; D002118:Calcium; D009638:Norepinephrine; D013324:Strontium