Evidence for increased release of prostaglandins of E-type in response to orthodromic stimulation in the guinea-pig superior cervical ganglion

In this study we have demonstrated that noradrenaline increases the levels of prostaglandin E2 and prostaglandin I2 (detected as the stable metabolite 6-keto-prostaglandin F1 alpha) synthesized by homogenates of superior cervical ganglia from the adult rat. This noradrenaline-induced prostaglandin production was further characterized: (a) Selective destruction of adrenergic sympathetic postganglionic neurons in the ganglia using 6-hydroxydopamine abolished both basal and stimulated prostaglandin production. (b) Elimination of preganglionic cholinergic sympathetic nerve terminals in the ganglia had no effect. (c) Mepacrine (a phospholipase inhibitor) and indomethacin (a cyclooxygenase inhibitor) attenuated both basal and stimulated prostaglandin production. (d) Yohimbine, but not prazosin, suppressed the noradrenaline dose-response curve for prostaglandin production. The results of these experiments show that, in vitro, noradrenaline stimulates de novo synthesis of prostaglandin E2 and prostaglandin I2 by sympathetic postganglionic neurons. This stimulation by noradrenaline appears to result from action at an alpha 2-adrenergic receptor.

mentioning

confidence: 99%

Noradrenaline‐Induced Prostaglandin Production by Sympathetic Postganglionic Neurons Is Mediated by α₂‐Adrenergic Receptors

Gonzales

Sherbourne

Goldyne

et al. 1991

“…Its involvement in generation of pyrogenic fever has been repeatedly proposed (Milton and Wendlandt, 197 1;Feldberg and Gupta, 1973;Coceani et al, 1985), and its mediatory role in norepinephrine-stimulated release of luteinizing hormone-releasing hormone has been established recently (Ojeda et al, 1979(Ojeda et al, , 1982Dray et al, 1985). PGE2 has also been proposed as a negative feedback modulator of neurotransmitter release in various systems (Hedqvist, 1977; Hillier and Templeton, 1980;Trevisani et al, 1982). However, the cell(s) and enzymes responsible for its formation in neural tissues have not been identified.…”

mentioning

confidence: 99%

Purification and Properties of Prostaglandin H‐E Isomerase from the Cytosol of Human Brain: Identification as Anionic Forms of Glutathione S‐Transferase

Ogorochi

Ujihara

Narumiya

1987

Prostaglandin H-E isomerase (EC 5.3.99.3) was purified from human brain cytosol. Purification was by ammonium sulfate fractionation, diethylaminoethyl-Sepharose chromatography, gel filtration on a BioGel P-100 column, GSH-agarose chromatography, and MonoQ chromatography. The activity was eluted in two peaks from the MonoQ column, which were designated peaks 1 and 2. The molecular weights of peaks 1 and 2, determined by gel filtration, were 42,000 and 44,000, respectively. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, peak 1 showed two bands at the molecular weights of 24,500 and 25,000, and peak 2 showed a single band at the molecular weight of 25,000, results suggesting that both were dimeric proteins. The pI values of both enzymes were approximately 5.4. The enzymes catalyzed selective conversion of prostaglandin H2 to prostaglandin E2. The Km values for prostaglandin H2 of peaks 1 and 2 were 147 and 308 microM, respectively, and the Vmax values were 380 and 720 nmol/min/mg of protein, respectively. GSH was required for the catalysis of both enzymes, and no other sulfhydryl compounds could support the reaction. A part of glutathione S-transferase (EC 2.5.1.18) was copurified with peaks 1 and 2 of prostaglandin H-E isomerase. Prostaglandin H-E isomerase activity of peak 2 enzyme was competitively inhibited by 1-chloro-2,4-dinitrobenzene, a substrate of glutathione S-transferase. These results suggested that prostaglandin H-E isomerases in human brain cytosol were identical with anionic forms of glutathione S-transferase.

“…Because cyclic AMP is believed to play a role in synaptic transmission in the superior cervical ganglion (SCG) (Greengard and Kebabian, 1974;Libet, 1979), there is much interest in understanding the control of cyclic AMP levels in this tissue. A number of neurotransmitters and hormones, including catecholamines, histamine, vasoactive intestinal peptide, and prostaglandins E l and E2, have been reported to raise cyclic AMP levels in the SCG of the rat (Cramer et al, 1973;Lindl and Cramer et al, 1974;Brown et al, 1979;Lindl, 1979;Quenzer et al, 1979;Volle and Patterson 1982;Trevisani et al, 1982). These substances are thought to act by stimulating a receptor-linked adenylate cyclase [ATPpyrophosphate lyase (cyclizing); EC 4.6.1.11 in the SCG, but direct stimulation has not been demonstrated.…”

mentioning

confidence: 99%

Adenylate Cyclase Activity in the Superior Cervical Ganglion of the Rat

Cahill¹,

Perlman²

1983

Adenylate cyclase activity in cell-free homogenates of the rat superior cervical ganglion (SCG) was assayed under a variety of experimental conditions. Adenylate cyclase activity was decreased by approximately one-half when 1 mM EGTA was included in the homogenization buffer and assay mixture, indicating the presence of a Ca2+-sensitive adenylate cyclase in the ganglion. In the presence of EGTA, basal adenylate cyclase activity in homogenates of the SCG was 12.9 +/- 0.6 pmol cyclic AMP/ganglion/10 min. Enzyme activity was stimulated three- to fourfold by 10 mM NaF or 10 mM MnCl2. Both GTP and its nonhydrolyzable analog guanylylimidodiphosphate (GppNHp) stimulated adenylate cyclase in a concentration-dependent manner over the range of 0.1-10.0 microM. Stimulation by GppNHp was five to six times greater than that produced by GTP at all concentrations tested. Decentralization of the ganglion had no effect on basal or stimulated adenylate cyclase activity. Receptor-linked stimulation of adenylate cyclase was not obtained with any of the following: isoproterenol, epinephrine, histamine, dopamine, prostaglandin E2, or vasoactive intestinal peptide. Thus the receptor-linked regulation of adenylate cyclase activity appears to be lost in homogenates of the ganglion.