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)