title: Alpha adrenoceptor activation and postreceptor contractile mechanisms in the human digital artery.
abstract: In order to compare postreceptor mechanisms of different alpha adrenoceptors, polyphosphoinositide hydrolysis and extracellular calcium entry stimulated by alpha-1 and alpha-2 adrenoceptor activation has been evaluated in the human digital artery, a tissue which contains both receptors. [3H]Inositol-I-PO4 accumulation during a 60-min exposure to an alpha-1 or alpha-2 agonist in the presence of 5 mM LiCl was used as an index of phosphatidylinositol-4,5-bisphosphate hydrolysis. Norepinephrine (1-30 microM) produced a concentration-related increase in [3H]inositol phosphate formation with an EC50 of 2.3 microM. Equieffective contractile concentrations of TL-99 (1 microM) and methoxamine (100 microM) produced similar increases in [3H]inositol-I-PO4 formation (1.41- and 1.70-fold increases over control, respectively). Norepinephrine EC50 values of 0.54, 1.7 and 1.0 microM were obtained for contractile responses in 1.25 mM Ca++, 0 mM Ca++ and 0 mM Ca++ + 0.1 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, respectively. Calcium omission (no ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid) produced similar inhibition of alpha-2 and alpha-1 adrenoceptor-mediated responses, assessed as inhibition of the area under the concentration-effect curve. Calcium omission generally produced a slightly greater inhibition of TL-99- or methoxamine-induced contractile responses than did nifedipine (0.1 or 1 microM), but the combination of calcium-omission and nifedipine practically abolished the contractile responses. However, the combination of a calcium omission and nifedipine did not prevent the accumulation of inositol monophosphate stimulated by TL-99 or methoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors.forename: M J
authors.initials: MJ
authors.lastname: Stevens
authors.forename: R F
authors.initials: RF
authors.lastname: Moulds
mesh_terms: D002118:Calcium / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004533:Egtazic Acid / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism; D008729:Methoxamine / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D013764:Tetrahydronaphthalenes; D004533:Egtazic Acid; C016893:2-(N,N-dimethylamino)-6,7-dihydroxytetralin; D008729:Methoxamine; D009543:Nifedipine; D002118:Calcium; D009638:Norepinephrine