Effects of prostaglandins E1, E2 and F2α on cyclic AMP levels in brainin vivo

Wellmann, W.; Schwabe, Ulrich

doi:10.1016/0006-8993(73)90275-8

Cited by 46 publications

(12 citation statements)

References 17 publications

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“…Separately, the maintenance of hyperalgesia in inflammatory and neuropathic pain states is known to be largely regulated by the activation of the cAMP signaling pathway (44)(45)(46). In the brain, intracellular cAMP level is known to rise rapidly in response to inflammation mainly because the cox-2 product PGE 2 activates E-prostanoid receptors and initiates a cascade of events beginning with stimulation of adenylate cylase (47). The resulting inflammatory pain can be blocked by an inactive cAMP analogue, which prevents PKA activation (48).…”

Section: Eets and Sehis Redirect Elevated Camp To An Analgesicmentioning

confidence: 99%

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

Inceoglu¹,

Jinks

Ulu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

218

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During inflammation, a large amount of arachidonic acid (AA) is released into the cellular milieu and cyclooxygenase enzymes convert this AA to prostaglandins that in turn sensitize pain pathways. However, AA is also converted to natural epoxyeicosatrienoic acids (EETs) by cytochrome P450 enzymes. EET levels are typically regulated by soluble epoxide hydrolase (sEH), the major enzyme degrading EETs. Here we demonstrate that EETs or inhibition of sEH lead to antihyperalgesia by at least 2 spinal mechanisms, first by repressing the induction of the COX2 gene and second by rapidly up-regulating an acute neurosteroid-producing gene, StARD1, which requires the synchronized presence of elevated cAMP and EET levels. The analgesic activities of neurosteroids are well known; however, here we describe a clear course toward augmenting the levels of these molecules. Redirecting the flow of pronociceptive intracellular cAMP toward up-regulation of StARD1 mRNA by concomitantly elevating EETs is a novel path to accomplish pain relief in both inflammatory and neuropathic pain states.cAMP ͉ inflammatory pain ͉ steroidogenesis

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Section: Eets and Sehis Redirect Elevated Camp To An Analgesicmentioning

confidence: 99%

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

Inceoglu¹,

Jinks

Ulu³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

172

218

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“…It has recently been reported that prostaglandins of the E series increase levels of cyclic AMP in brain tissue from the mouse and rat (Berti, Trabucchi, Bernareggi & Fumagalli, 1972;Kuehl et al 1973;Wellmann & Schwabe, 1973) but not from the guinea-pig, rabbit or man (Shimizu, Creveling & Daly, 1970;Berti et al 1972). In any case, cyclic AMP could not mediate the hyperthermic effect of prostaglandin in the cat since paracetamol and indomethacin, which inhibited cholera enterotoxin-and dibutyryl cyclic AMP-induced increases in body temperature in the present study, have previously been shown not to inhibit prostaglandin El-induced hyperthermia in this species (Milton & Wendlandt, 1971;Milton, 1973; Clark, W. G. & Cumby, H. R., unpublished).…”

Section: Discussionmentioning

confidence: 99%

The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat

Clark¹,

Cumby²,

Davis³

1974

The Journal of Physiology

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SUMMARY1. Cholera enterotoxin was used to evaluate a possible role of endogenous cyclic AMP in production of hyperthermia. Injection of purified toxin (0-10-10 ,ug in 0t10 ml.) into the lateral cerebral ventricle of unanaesthetized cats caused dose-related hyperthermic responses. Heating the toxin for 40 min at 900 C abolished its hyperthermic activity.2. Intraventricular administration ofdibutyryl cyclic AMP (250-1000 ltg) also caused hyperthermia which, however, was preceded by transient periods of hypothermia and/or excitation in about half of the tests.3. Paracetamol, indomethacin and sodium salicylate inhibited hyperthermic responses to cholera enterotoxin. Paracetamol and indomethacin also inhibited hyperthermia induced by dibutyryl cyclic AMP (sodium salicylate was not tested).4. It is likely that the hyperthermic effect of cholera enterotoxin in the cat is mediated via endogenous cyclic AMP and that the antipyretics inhibit this effect by an action subsequent to the increase in cyclic AMP.5. It is unlikely that prostaglandin-induced hyperthermia in the cat is mediated via cyclic AMP since these antipyretics do not inhibit this response to prostaglandin E1.

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“…The study was then extended to drugs affecting other brain amines (Collier, Hammond & Schneider, 1974). Because of the interaction of some amines with cyclic nucleotides (Weiss & Costa, 1968;Ferrendelli, Steiner, McDougal & Kipnis, 1970;Wellman & Schwabe, 1973;Daly, 1975) and because another drug of dependence, morphine, interacts with cyclic nucleotides (Coffier & Roy, 1974;Gullis, Traber & Hamprecht, 1975), we then studied the effects of some other drugs affecting cyclic nucleotide mechanisms on the incidence of head twitches after ethanol withdrawal. These studies are described in detail below; some of these findings have been briefly reported (Hammond & Schneider, 1973; Coffier, Hammond & Schneider, 1976).…”

Section: Introductionmentioning

confidence: 99%

Effects of Drugs Affecting Endogenous Amines or Cyclic Nucleotides on Ethanol Withdrawal Head Twitches in Mice

Collier

Hammond

Schneider

1976

British J Pharmacology

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1 Twenty-four hours after ethanol withdrawal, dependent mice exhibited frequent head twitching. Naive mice exhibited similar twitching 15 min after treatment with 5-hydroxytryptophan (5-HTP) or 6 h after a-methyl-p-tyrosine (AMPT). Ethanol lessened the incidence of head twitches induced by any of these treatments. 5-HTP and AMPT each increased the incidence of head twitches induced by withdrawal of ethanol from dependent mice. 2 Drugs that affect the amount or activity of endogenous amines or cyclic nucleotides modified the incidence of head twitches. Nearly all drugs acted in the same direction on twitching elicited by any of these three treatments.3 The incidence was lessened by: (a) methysergide, methergoline, MA 1420, p-chlorophenylalanine and p-chloroamphetamine; (b) dopamine, noradrenaline, L-DOPA, amphetamine and apomorphine; (c) hyoscine and nicotine; and (d) adenosine triphosphate, dibutyryl cyclic adenosine-3',5'-monophosphate (db cyclic AMP) and prostaglandins El and E2.4 The incidence was increased by: (a) acetylcholine, carbachol and physostigmine; and (b) guanosine triphosphate, dibutyryl cyclic guanosine monophosphate (db cyclic GMP), theophylline and 3-isobutyl-l-methyl-xanthine. 5 These findings suggest that head twitching induced by these three treatments arises from a common biochemical mechanism, which may ultimately be a change in favour of cyclic GMP of the balance between this nucleotide and cyclic AMP within appropriate neurones. This imbalance appears to be elicited or increased by 5-hydroxytryptamine and acetylcholine and to be decreased by dopamine, noradrenaline and E prostaglandins. 6 Neither actinomycin D nor cycloheximide, given during the induction of ethanol dependence, altered the incidence of head twitches after ethanol withdrawal.

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Effects of prostaglandins E1, E2 and F2α on cyclic AMP levels in brainin vivo

Cited by 46 publications

References 17 publications

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

Soluble epoxide hydrolase and epoxyeicosatrienoic acids modulate two distinct analgesic pathways

The hyperthermic effect of intracerebroventricular cholera enterotoxin in the unanaesthetized cat

Effects of Drugs Affecting Endogenous Amines or Cyclic Nucleotides on Ethanol Withdrawal Head Twitches in Mice

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