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D Piomelli

Publications and source records attributed to D Piomelli.

80 records · Page 5Linked to original sources
PubMed1987

Metabolites of arachidonic acid in the nervous system of Aplysia: possible mediators of synaptic modulation.

Release of arachidonic acid from membrane phospholipids is receptor-mediated and might generate second messengers in neurons. We tested this idea using the simple nervous system of the marine mollusk, Aplysia californica. Aplysia neural components metabolize arachidonic acid through lipoxygenase and cyclo-oxygenase pathways. We identified 2 major lipoxygenase products, 12- and 5-hydroxyeicosatetraenoic acids (12-HETE and 5-HETE), and 2 cyclo-oxygenase products, PGE2 and PGF2 alpha. These metabolites of arachidonic acid are formed in synaptosomes, as well as in identified nerve cell bodies, indicating that both lipoxygenase and cyclo-oxygenase pathways are active within neurons. Application of the modulatory neurotransmitter histamine to cerebral ganglia that had been labeled with 3H-arachidonic acid induced the formation of 3H-12-HETE. This response was inhibited by the histamine antagonist cimetidine. Furthermore, release of radioactive 5-HETE and 12-HETE was observed after intracellular stimulation of the histaminergic cell C2 in cerebral ganglia labeled with 3H-arachidonic acid. Cimetidine also inhibited this response. Application of serotonin or stimulation of the giant serotonergic cell (GCN) in the cerebral ganglion did not cause detectable amounts of the labeled eicosanoids to be released. We found that intracellular stimulation of putative histaminergic neurons in the L32 cluster of the abdominal ganglion, which produces presynaptic inhibition in L10 neurons, also elicited the release of 3H-12-HETE and 3H-PGE2. Thus, for the first time we provide evidence that synaptic stimulation promotes turnover of arachidonic acid in neurons. We suggest that metabolites of arachidonic acid are likely to participate in some postsynaptic responses to histamine and may be second messengers for presynaptic inhibition.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1987

Leukotriene biosynthesis by canine and human coronary arteries.

Canine and human epicardial coronary arteries were tested for their ability to metabolize exogenous arachidonic acid to lipoxygenase products. Unextracted medium from incubations of canine or human arteries with arachidonic acid and the calcium ionophore, A23187, contained a substance which exhibited a leukotriene (LT)-like smooth muscle contracting activity when tested on the superfused guinea pig lung parenchymal strip bioassay. This activity could be blocked by the LT antagonist, FPL-55712. Compounds present in these media were purified by high-performance liquid chromatography and identified as LTC4, LTD4 and LTE4 by liquid scintillation counting, bioassay and radioimmunoassay. In addition, coronary artery rings converted synthetic [3H]LTC4 to [3H]LTD4 with a half-life of 44 +/- 8 min. LTD4 metabolism to LTE4 was also demonstrated. The metabolism of [3H]LTC4 was abolished by incubation of the arterial rings with a gamma-glutamyl transpeptidase inhibitor, serineborate. Production of monohydroxyeicosatetraenoic acids (5-, 12- and 15-HETE) which have been isolated previously from vascular tissue incubations was confirmed. Production of HETE was inhibited by nordihydroguaiaretic acid and unaffected by indomethacin. These findings indicate that coronary vessels can metabolize exogenous arachidonic acid by the lipoxygenase pathway. In addition to HETE, the vessels were shown to synthesize LTC4, LTD4 and LTE4, compounds which possess potent biological actions on the coronary circulation.

Animals↗
PubMed1984

The cyclo-oxygenase pathway in the avascular heart of the frog, Rana esculenta L.

A modification of Vane's cascade is reported, allowing the superfusion bioassay of prostaglandin-like substances (PLS) in the outflow of isolated and perfused heart of the frog Rana esculenta L. Using both this technique and radioimmunoassay determination, the cyclo-oxygenase pathway in perfused frog heart has been investigated. Arachidonate (AA) (2-20 micrograms) injected into the perfusing fluid, was transformed by the heart into PLS, as shown by the response of the bioassay tissues (rat stomach strip, chick rectum, rat colon). A compound capable of relaxing rabbit mesenteric artery and a rabbit aorta contracting substance were also generated. The release was inhibited by indomethacin (1.0 X 10(-5)M). Radioimmunoassay determination of PGE2, TXB2 and 6-keto-PGF1 alpha in frog heart effluent, before and after AA injection (20 micrograms), gave the following yields (ng/ml of effluent). Basal: PGE2 = 0.45 +/- 0.15; TXB2 = 0.46 +/- 0.13; 6-keto-PGF1 alpha = 2.21 +/- 0.3. Following AA: PGE2 = 1.55 +/- 0.35; 6-keto-PGF1 alpha = 3.4 +/- 0.4; TXB2 = 1.00 +/- 0.06. Our results suggest that prostacyclin is a major product of the cyclo-oxygenase pathway in frog perfused heart. The biological significance of this finding is discussed in relation to both the absence of a coronary circulation in amphibians and to the spongy nature of frog myocardium.

Animals↗
PubMed1983

Vasoconstrictory effects of adrenalin on the perfused head of the eel (Anguilla anguilla L.).

Adrenalin (5.0 X 10(-5) M) increases gill vascular resistance up to 23.2 +/- 6.8% in the isolated and perfused head of the european eel (Anguilla anguilla L.). This vasoactive response is nearly abolished by the alpha-adrenergic blocking agent phentolamine mesylate (5.0 X 10(-5) M), while it is increased by the beta-blocker propranolol (5.0 X 10(-4) M). From these results it may be inferred that, in our experimental conditions, the major response to the catecholamine is a vasoconstriction mediated via alpha-adrenoceptors.

Animals↗
PubMed1983

Different distribution of serotonin in an elasmobranch (Scyliorhinus stellaris) and in a teleost (Conger conger) fish.

1. A comparative quantitative study on the occurrence of 5-HT in several tissues and organs of the elasmobranch Scyliorhinus stellaris and the teleost Conger conger has been carried out. 2. In Scyliorhinus, the richest source of the amine is the brain, in which 5-HT is twice as concentrated as in the teleost brain. Significant levels have been also detected in the intestine, followed by gills and heart. 5-HT is also concentrated in other epithelial organs, such as the rectal gland and the olfactory organ. 3. In Conger, the gills show the highest content of 5-HT, in which, like in the kidney, serotonin is 2-3 times more concentrated than in the corresponding organs of the elasmobranch. 4. These differences are discussed in relation to the distinct phylogenetic and ecophysiological features of the two animals. In addition, the possible functional significance of 5-HT in the fish heart is taken into consideration.

Animals↗
PubMedDate not supplied

Presence of depolarization-induced suppression of inhibition in a fraction of gabaergic synaptic connections in rat neocortical cultures.

Brief depolarization of postsynaptic neurons in hippocampus and cerebellum results in a transient depression of GABAergic inhibitory input, called "depolarization-induced suppression of inhibition" (DSI). We studied whether a similar phenomenon occurs in the rat neocortical neurons. Using patch-clamp technique in neocortical cell cultures we examined the effects of a 5-second depolarization of postsynaptic neurons on evoked GABAergic inhibitory post-synaptic currents (IPSCs). We found that the depolarization evoked a suppression of IPSC amplitude in 6 out of 26 neuronal pairs tested. The suppression of IPSC amplitude lasted for approximately 70 seconds and was accompanied by changes of paired-pulse ratio and IPSC coefficient of variation (CV), which is suggestive of a presynaptic mechanism. These results are in agreement with previous observations in hippocampal cell cultures and suggest that neocortical neurons express DSI.

Animals↗
PubMedDate not supplied

Dopamine D2 receptor signaling via the arachidonic acid cascade: modulation by cAMP-dependent protein kinase A and prostaglandin E2.

Recent studies have shown that, in Chinese hamster ovary cells transfected with D2-receptor cDNA, CHO(D2) cells, D2 agonists are potent in enhancing the release of [3H]arachidonic acid (AA) induced by stimulation of constitutive purinergic receptors or by application of Ca2+ ionophores. This facilitatory action is further amplified by the concomitant activation of D1 receptors, which per se have no effect on evoked [3H]AA release. Here, we review a series of experiments aimed at examining the molecular mechanism of this synergistic interaction. The results show that, in CHO(D2) cells: (a) application of 8-Br-cAMP or stimulation of constitutive prostaglandin (PG)E2 receptors augment the AA response produced by D2 agonists; (b) in CHO(D2) cells transfected with human beta 2-receptor cDNA, the beta-agonist, isoproterenol, produces a similar effect; (c) the potentiation of [3H]AA release produced by PGE2 and 8-Br-cAMP is prevented by overexpressing either a protein inhibitor of cAMP-dependent protein kinase (PKA) or a mutated form of pKA regulatory subunit incapable of binding cAMP; (d) mock-synergism is obtained in CHO(D2) cells overexpressing the catalytic subunit of PKA; (e) PGE2 is a major AA metabolite in stimulated CHO(D2) cells and its formation may contribute to the effect of D2 agonists on AA release. The results indicate that cAMP-induced activation of PKA represents a likely molecular basis for D1/D2 receptor synergism on AA release. They also suggest that additional membrane receptors, colocalized with D2 and positively linked to adenylyl cyclase, may exert a similar action. Furthermore, stimulation of PGE2 receptors by endogenously produced prostaglandin may participate in AA signaling at the D2 receptor, by providing a paracrine positive feedback loop.

Animals↗