Intracellular Ca2+ elevation and contraction due to prostaglandin F2alpha in rat aorta.

Prostaglandin F2alpha was tested to determine (a) whether its effect on intracellular Ca2+ levels ([Ca2+]i) and force in vascular smooth muscle was mediated through activation of the thromboxane A2 and/or prostaglandin receptor, and (b) the relative roles of Ca2+ influx via L-type and non-L-type Ca2+ channels in prostaglandin receptor-mediated contraction. [Ca2+]i and force were measured simultaneously in fura-2-loaded rat aortic strips. The thromboxane A2 receptor antagonist, SQ29548 ([1S]-1a,2b(5Z),3b,4a-7-(3-[2-[(phenylamino)carbonyl] hydrazinomethyl)-7-oxobicyclo-[2.2.1]hept-2-yl-5-heptenoic acid), prevented the prostaglandin F2alpha-induced plateau [Ca2+]i elevation and force by 80-90%, while abolishing these responses due to the thromboxane A2 receptor agonist, U46619 (9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F2alpha). Prostaglandin F2alpha (+ SQ29548)-induced plateau [Ca2+]i elevation and force were not inhibited by verapamil. Ni2+, a non-selective cation channel blocker, in the presence of verapamil, abolished the prostaglandin F2alpha (+ SQ29548)-elevated [Ca2+]i, while the contraction was only partially inhibited. These results suggest that, in rat aorta, (1) elevated [Ca2+]i and force due to high prostaglandin F2alpha concentrations largely results from thromboxane A2 receptor activation, and (2) the prostaglandin component of the prostaglandin F2alpha-induced contraction is dependent on Ca2+ influx via non-L-type channels.

[1]  S. Narumiya,et al.  International Union of Pharmacology classification of prostanoid receptors: properties, distribution, and structure of the receptors and their subtypes. , 1994, Pharmacological reviews.

[2]  H. Ozaki,et al.  Ca2(+)-dependent and independent mechanisms of sustained contraction in vascular smooth muscle of rat aorta. , 1990, Japanese journal of pharmacology.

[3]  S. Miyamoto,et al.  Different pathways of calcium sensitization activated by receptor agonists and phorbol esters in vascular smooth muscle , 1993, British journal of pharmacology.

[4]  H. Arita,et al.  A common binding site for primary prostanoids in vascular smooth muscles: a definitive discrimination of the binding for thromboxane A2/prostaglandin H2 receptor agonist from its antagonist. , 1989, Biochimica et biophysica acta.

[5]  T. Tsuchiya,et al.  Receptor agonists induce myosin phosphorylation-dependent and phosphorylation-independent contractions in vascular smooth muscle. , 1992, The Journal of pharmacology and experimental therapeutics.

[6]  G. Dorn,et al.  Dissociation of the contractile and hypertrophic effects of vasoconstrictor prostanoids in vascular smooth muscle. , 1992, The Journal of biological chemistry.

[7]  J. Balwierczak The relationship of KCl‐ and prostaglandin F2α‐mediated increases in tension of the porcine coronary artery with changes in intracellular Ca2+measured with fura‐2 , 1991, British journal of pharmacology.

[8]  N. Morel,et al.  Characterization in rat aorta of the binding sites responsible for blockade of noradrenaline‐evoked calcium entry by nisoldipine , 1991, British journal of pharmacology.

[9]  K. Okumura,et al.  Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. , 1990, Hypertension.

[10]  W. Abebe,et al.  Simultaneous measurement of intracellular calcium and tension in vascular smooth muscle: validation of the everted ring preparation. , 1995, Journal of pharmacological and toxicological methods.

[11]  R. Rapoport Potentiation of norepinephrine-induced contraction by primary prostaglandin receptor activation in rat aorta. , 1993, European journal of pharmacology.

[12]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[13]  T. Hallam,et al.  Use of manganese to discriminate between calcium influx and mobilization from internal stores in stimulated human neutrophils. , 1989, The Journal of biological chemistry.

[14]  I. Takayanagi,et al.  Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura‐2 , 1990, British journal of pharmacology.

[15]  H. Ozaki,et al.  Changes in cytosolic calcium level in vascular smooth muscle strip measured simultaneously with contraction using fluorescent calcium indicator fura 2. , 1988, The Journal of pharmacology and experimental therapeutics.

[16]  R. Rapoport Effects of norepinephrine on contraction and hydrolysis of phosphatidylinositols in rat aorta. , 1987, The Journal of pharmacology and experimental therapeutics.