Alpha adrenoceptor activation and postreceptor contractile mechanisms in the human digital artery.
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)
Stevens
M J
MJ
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
Moulds
R F
RF
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
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