Summary
Rabbit splenic capsular strips released PGE2 when contracted by noradrenaline. Contraction as well as PGE2-release were Ca2+-dependent.
In the presence of Ca2+ the ionophore A 23187 induced a long lasting contraction and a vigorous PGE2-release. In Ca2+-free medium the ionophore was ineffective. Introduction of Ca2+ to splenic strips preincubated with the ionophore in the absence of Ca2+ reinstalled contracture and PGE2-relase.
The PGE2-release induced by the PG-precursor arachidonic acid was Ca2+-independent.
Addition of phospholipase A to splenic strips elicited a strong PGE2-release.
These results indicate, that the first step of stimulus evoked PG-release is the Ca2+-mediated activation of phospholipase A2. This enzyme liberates from membrane bound phospholipids C-20-fatty acids, which then serve as substrates for the PG-synthetizing enzymes. Therefore the rate limiting step in stimulusevoked PG-release seems to be rather the phospholipase A2 activity than the state of activation of one of the PG-synthetizing enzymes.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bartels, J., Kunze, H., Vogt, W., Wille, G.: Prostaglandins: Liberation from and formation in perfused frog intestine. Naunyn-Schmiedeberg's Arch. Pharmacol. 266, 199–207 (1970)
Cochrane, D. E., Douglas, W. W.: Depolarizing effects of the ionophores X-537A and A23187 and their relevance to secretion. Br. J. Pharmacol. 54, 400–402 (1975)
Cochrane, D. E., Douglas, W. W., Mouri, T., Nakazato, Y.: Calcium and stimulus-secretion coupling in the adrenal medulla: Contrasting stimulating effects of the ionophore X-537A and A 23187 on catecholamine output. J. Physiol. (Lond.) 252, 363–378 (1975)
Diekmann, J. M., Jobke, A., Peskar, B. A., Hertting, G.: Angiotensin II-induced contractions of rabbit splenic capsular strips and release of prostaglandins. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 177–183 (1977)
Ferreira, S. H., Moncada, S., Vane, J. R.: Some effects of inhibiting endogenous prostaglandin formation on the responses of the cat spleen. Br. J. Pharmacol. 47, 48–58 (1973)
Ferreira, S. H., Herman, A. G., Vane, J. R.: Prostaglandin production by rabbit isolated jejunum and its relationship to the inherent tone of the preparation. Br. J. Pharmacol. 56, 469–477 (1976)
Flower, R. J., Blackwell, G. J.: The importance of phospholipase A2 in prostaglandin biosynthesis. Biochem. Pharmacol. 25, 285–291 (1976)
Gilmore, N., Vane, I. R., Wyllie, J. H. Prostaglandins released by the spleen. Nature 218, 1135–1140 (1968)
Hayne, B., Champion, S., Jacquemin, C.: Control by TSH of a phospholipase A2 activity, a limiting factor in the biosynthesis of prostaglandins in the thyroid. FEBS Lett. 30, 253–259 (1973)
Jobke, A., Peskar, B. A., Peskar, B. M.: On the specificy of antisera against prostaglandin A2 and E2. FEBS Lett. 37, 192–196 (1973)
Jobke, A., Peskar, B. A., Hertting, G.: On the relation between release of prostaglandins and contractility of rabbit splenic capsular strips. Naunyn-Schmiedeberg's Arch. Pharmacol. 292, 35–42 (1976)
Kunze, H.: Formation of 1-14C-prostaglandin E2 and two prostaglandin metabolites from 1-14C-arachidonic acid during vascular perfusion of the frog intestine. Biochim. Biophys. Acta 202, 180–183 (1970)
Kunze, H., Vogt, W.: Significance of phospholipase A for prostaglandin formation. Ann. N.Y. Acad. Sci. 180, 123–125 (1971)
Kunze, H., Bohn, E., Vogt, W.: Effects of local anaesthetics on prostaglandin biosynthesis in vitro. Biochim. Biophys. Acta 360, 260–269 (1974)
Lands, W. E. M., Rome, L. H.: Inhibition of prostaglandin biosynthesis. In: Prostaglandins: Chemical and biochemical aspects (Advances in prostaglandin research) S. M. M. Karim, ed.), pp. 88–92. Baltimore: University Park Press 1976
Lands, W. E. M., Samuelsson, B.: Phospholipid precursors of prostaglandins. Biochim. Biophys. Acta 164, 426–429 (1968)
Lembeck, F., Popper, H., Juan, H.: Release of prostaglandins by bradykinin as an intrinsic mechanism of its algesic effect. Naunyn-Schmiedeberg's Arch. Pharmacol. 294, 69–73 (1976)
McMurray, W. C., Magee, W. L.: Phospholipid metabolism. Ann. Rev. Biochem. 41, 129–160 (1972)
Ogawa, Y.: The apparent binding constant of glycoletherdiaminetetraacetic acid for calcium at neutral pH. J. Biochem. (Tokyo) 64, 255–257 (1968)
Peskar, B., Hertting, G.: Release of prostaglandins from isolated cat spleen by angiotensin and vasopressin. Naunyn-Schmiedeberg's Arch. Pharmacol. 279, 227–234 (1973)
Piper, P. J., Vane, J. R.: The release of prostaglandins from lung and other tissues. Ann. N.Y. Acad. Sci. 180, 363–385 (1971)
Pressman, B. C.: Carboxylic ionophores as mobile carriers for divalent ions. In: The role of membranes in metabolic regulation (M. A. Mehlman and R. W. Hanson, eds.), pp 149–164. New York: Academic Press 1972)
Reed, P. W., Lardy, H. S.: A 23187: A divalent cation ionophore. J. Biol. Chem. 247, 6970–6977 (1972)
Vogt, W.: Role of phospholipase A2 in prostaglandin formation. In: Advances in prostaglandin and thromboxane research, Vol. 3 (C. Galli et al., eds.), pp. 89–95. New York: Raven Press 1978
Vonkeman, H., van Dorp, D. A.: The action of prostaglandin syndthetase on 2-arachidonyl-lecithin. Biochim. Biophys. Acta 164, 430–432 (1968)
Author information
Authors and Affiliations
Additional information
This work was supported by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 70
Rights and permissions
About this article
Cite this article
Förstermann, U., Hertting, G. The importance of Ca2+-mediated phospholipase A2 activation for stimulus-evoked PGE2-release from rabbit splenic capsular strips. Naunyn-Schmiedeberg's Arch. Pharmacol. 307, 243–249 (1979). https://doi.org/10.1007/BF00505940
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00505940