Inhibition of α-receptor-induced Ca 2+ release and Ca 2+ influx by Mn 2+ and La 3+

Abstract

The influence of Mn 2+ and La 3+ on α-receptor-stimulated Ca 2+ movements was examined in arterial smooth muscle of the rabbit aorta. Both cations cause an inhibition of phenylephrine (PE) contractile response which exhibits a different pattern at low and high cation concentrations. At 0.1-1.0 nM inhibition by Mn 2+ and La 3+ was predominately due to a reduction in Ca 2+ influx reflected as inhibition of the slow phase of contraction and reduction in PE-stimulated 45Ca uptake. PE log dose-response curves were shifted to the right in a non-parallel manner by 1 mN Mn 2+ such that responses to lower PE concentrations were more inhibited. However, in the presence of 10 mM Mn 2+ PE responses are equally inhibited at all PE levels. At 10 mM both Mn 2+ and La 3+ also inhibited PE-stimulated Ca 2+ release resulting in a reduction in both the rapid phase of contraction and in the magnitude of PE stimulation of 45Ca efflux. The effects of Mn 2+ (1 or 10 mM) on contraction and 45Ca efflux were rapidly reversible, while the effect of La 3+ was not. Inhibition of Ca 2+ release by 10 mM Mn 2+ was not caused by displacement of releasable Ca 2+, but appeared to reflect their occupation of a superficially located receptor modulating site. The inhibition of Ca 2+ influx by lower concentrations of Mn 2+ may illustrate the functional consequence of configurational changes in the α 2-form of the receptor which have been recently described at lower concentrations of divalent cations.