Calcium Utilization Associated with U-46619 and PGF2a Vascular Responses in Rat Lungs

Abstract

The pulmonary vasoconstrictor responses to U-46619 and PGF_2a are calcium dependent. The purpose of this investigation was to determine to what extent extracellular and intracellular calcium pools are utilized during the dose-de pendent pulmonary vasopressor responses induced by multiple doses of U- 46619 and PGF_2a. Increasing doses of these agonists were administered to isolated rat lungs perfused with Krebs-Ringer bicarbonate (KRB) or KRB not containing CaCL ₂. The data indicate that U-46619 uses predominantly extracel lular calcium at low doses (0.1 μg) and depends solely on intracellular calcium at the highest dose (0.4 μg). In contrast PGF _2a appears to use depletable intracellu lar calcium stores to achieve contraction.

Get full access to this article

View all access options for this article.

References

Movesian M. : Calcium physiology in smooth muscle. Prog Cardiovasc Dis 25:211-223, 1982.

Van Breeman C. , Aaronson P. , Lontzenhiser R. , et al: Ca2+ movements in smooth muscle. Chest 78:157-165, 1980.

Van Breeman C. , Saida K. : Cellular mechanisms regulating [Ca2+] smooth muscle. Ann Rev Physiol 51:315-329, 1989.

Morgan KG , Bradley A. , Defeo TT : Calcium transients in smooth muscle. Ann NY Acad Sci 522:328-337, 1988.

Otani H. , Sugimoto J. , Mariata M. : Mobilization of intracellular calcium as a mechanism for the positive inotropic effect by prostaglandin F2a in isolated guinea pig atria . Prosta Leuko Med 24:51-56, 1986.

Van Breeman C. , Saida K. , Yamamoto H. , et al: Vascular smooth muscle sarcoplasmic reticulum, function and mechanisms of Ca2+ release. Ann NY Acad Sci 522:60-73, 1988.

Angerio AD , Fitzpatrick TM , Kot PA , et al: Effect of verapamil on the pulmonary vasoconstrictor action of prostaglandin F2a and a synthetic prostaglandin H2 analogue . Br J Pharm 73:101-103, 1981.

Angerio AD , Fitzpatrick TM , Kot PA , et al: Effect of TMB-8 on the pulmonary vasoconstrictor action of prostaglandin F2a and the thromboxane mimic, U-46619. Br J Pharm 77:55-58, 1982.

Santoian EC , Angerio AD , Fitzpatrick TM , et al: Effects of intracellular and extracellular calcium blockers on the pulmonary vascular responses to PGF2a and U-46619. Angiology 38:51-55, 1988.

10.

Stinger R. , Fitzpatrick TM , Corey E. , et al: Selective antagonism of prostaglandin F2a-mediated vascular responses to n-dimethylamino substitution of prostaglandin F 2a. J Pharm Exp Ther 220:521-525, 1982.

11.

Santoian EC , Angerio AD , Schneidkraut MJ , et al: Role of calcium in U-46619 and PGF 2a pulmonary vasoconstriction in rat lungs. Am J Physiol 257: H2001-H2005, 1989.

12.

Downes H. , Hirshman C. : Calcium chelators increase airway responsiveness. J Appl Physiol 59:92-95, 1985.

13.

Kern D. , Malik A. : Microvascular albumin permeability in isolated perfused lung: Effects of EDTA . J Appl Physiol 58:372-375, 1985.

14.

Berridge MJ : Inositol trisphosphate and diacylglyerol: Two interacting secondary messengers. Ann Rev Biochem 56:159-193, 1987.

15.

Rasmussen H. : The calcium messenger system. Part 1. N Engl J Med 314:1094-1100, 1986 .

16.

Rasmussen H. : The calcium messenger system. Part 2. N Engl J Med 314:1164-1170, 1986 .

17.

Davis JS , Weakland LL , Weiland DA , et al: Prostaglandin F2a stimulates phosphotidylinositol, 4,5-bis-phosphate hydrolysis and mobilizes intracellular CA2+ in bovine luteal cells. Proc Natl Acad Sci 84:3728-3732, 1987.

18.

Davis JS , Alila HW , West LA , et al: Second messenger systems and progesterone secretion of the bovine corpus luteum: Effects of gonadotropins and prostaglandin F2a. J Steroid Biochem 32:643-649, 1989.

19.

Orton EC , Raffestin B. , McMurty IF : Protein kinase C influences rat pulmonary vascular reactivity. Am Rev Respir Dis 141:654-658, 1990.