Inhibition of alpha-receptor-induced Ca2+ release and Ca2+ influx by Mn2+ and La3+ |
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Authors: | R Deth C Lynch |
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Affiliation: | Northeastern University, College of Pharmacy and Allied Health, Pharmacology Section, Boston, MA 02115, U.S.A. |
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Abstract: | The influence of Mn2+ and La3+ on alpha-receptor-stimulated Ca2+ 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 mM inhibition by Mn2+ and La3+ was predominately due to a reduction in Ca2+ 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 mM Mn2+ such that responses to lower PE concentrations were more inhibited. However, in the presence of 10 mM Mn2+ PE responses are equally inhibited at all PE levels. At 10 mM both Mn2+ and La3+ also inhibited PE-stimulated Ca2+ 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 Nm2+ (1 or 10 mM) on contraction and 45Ca efflux were rapidly reversible, while the effect of La3+ was not. Inhibition of Ca2+ release by 10 mM Mn2+ and La3+ was not caused by displacement of releasable Ca2+, but appeared to reflect their occupation of a superficially located receptor modulating site. The inhibition of Ca2+ influx by lower concentrations of Mn2+ may illustrate the functional consequence of configurational changes in the alpha 2-form of the receptor which have been recently described at lower concentrations of divalent cations. |
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Keywords: | Artery Calcium Manganese Lanthanum α-Adrenergic Smooth muscle |
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