Regulation of noradrenaline overflow in rat cerebral cortex by prostaglandin E2.

1 The effects of prostaglandin E2 (PGE2), PGF2 alpha and PGI2 and of inhibitors of prostaglandin synthesis and action, on the K+-evoked [3H]-noradrenaline ([3H]-NA) overflow from rat cerebral cortex slices have been investigated. 2 PGE2 reduced, while indomethacin (a prostaglandin synthesis inhibitor) or SC 19220 (a prostaglandin receptor antagonist) increased, the evoked overflow compared with controls. 3 The inhibition of [3H]-NA overflow by PGE2 was dose-dependently antagonized by SC 19220. 4 The results indicate that PGE2 modulates NA release in rat cerebral cortex in vitro.     

Prostaglandin E2, prostaglandin I2 and the vascular changes of inflammation.

1. Plasma exudation and blood flow changes induced by intradermal injection of prostaglandins E2 (PGE2), I2 (PG12), D2 (PGD2) and F2 alpha (PGF2 alpha) were measured in rabbit dorsal skin by the use of [131I]-albumin and 133Xe. 2. Little plasma exudation was produced by any of the prostaglandins when injected alone. 3. Both PGE2 and PGI2 were potent at increasing blood flow, whereas PGF2 alpha and PGD2 produced an increase only at high doses. 4. All of the prostaglandins studied potentiated the plasma exudation induced by bradykinin. PGE2 and PGI2 had similar potent potentiating activity, whereas PGD2 and PGF2 alpha had activity at doses too high to be of biological significance. 5. Intradermal injections of arachidonate alone resulted in little plasma exudation but produced an increase in blood flow. Arachidonate potentiated bradykinin-induced plasma exudation. 6. Locally-injected indomethacin had no effect on basal blood flow and little effect on the exudation produced by bradykinin, but indomethacin did inhibit the vasodilatation and exudation potentiation produced by arachidonate. 7. PGE2 and PGI2 had similar potency in producing marked potentiation of plasma exudation induced by intradermal injection of zymosan. 8. In the reaction to zymosan, it is concluded that vasodilatation is the result of the release of arachidonate, which is subsequently coverted to either PGE2 or PGI2. These substances regulate the plasma exudation induced by independently-released vascular permeability-increasing mediators.     

Pulmonary and systemic vascular effects of exogenous prostaglandin I2 in fetal lambs.

Effects of PGI2 upon pulmonary vascular resistance and systemic arterial pressure of near term fetuses were evaluated in anesthetized, exteriorized, unventilated fetal lambs by means of an open-chest, pump-perfused lung preparation. These effects were compared to those of PGE1 and PGE2 in the same animals. Intrapulmonary arterial infusions of PGI2 produced dose-dependent decreases in pulmonary vascular resistance and systemic arterial pressure. Effects of PGI2 upon pulmonary vascular resistance are intermediate with respect to those of PGE1 (greater) and PGE2 (less). PGI2 is a potent hypotensive compound when administered to fetal lambs, producing dose-dependent decreases in systemic arterial pressure. When the three prostaglandins are infused into the pulmonary artery, effects on systemic arterial pressure of PGE1 and PGI2 are nearly identical. Effects of PGE2 are considerably less. PGI2 is a potent dilator of fetal lamb vessels and could play a role in circulatory control during perinatal transition.     

Tromboxane B2 inhibits the pulmonary inactivation of prostaglandin E2 in the dog.

1 The systemic vasodepressor response to intravenously administered prostaglandin E2 (PGE2, 0.3, 1.0 and 3.0 micrograms/kg) is potentiated during intravenous infusion of thromboxane B2 (TXB2, 1.0 micrograms kg-1 min-1) in the anaesthetized dog. 2 The augmented haemodynamic response returns toward control values following cessation of the TXB2 infusion. 3 The systemic haemodynamic responses to intra-arterially administered PGE2, PGF2 alpha and PGI2 as well as intravenously administered PGF2 alpha and PGI2 are not altered by TXB2 infusion. 4. This study suggests that TXB2 inhibits the pulmonary inactivation of PGE2. 5 Arachidonic acid metabolites may interact, producing haemodynamic responses differing from their individual effects.     

Some direct and reflex cardiovascular actions of prostacyclin (PGI2) and prostaglandin E2 in anaesthetized dogs.

1 The aim of the study was to determine the mechanism of the hypotension and bradycardia produced by prostacyclin (PGI2). 2 Haemodynamic studies were carried out in nineteen open-chest beagle dogs anaesthetized with chloralose. PGI2 was infused intravenously or into the left atrium. 3 Infusions of PGI2 either intravenously or into the left atrium equally reduced arterial pressure and total peripheral resistance but bradycardia was greater after infusion into the left atrium. 4 Comparison of effects of PGI2 with those of prostaglandin E2 (PGE2) showed that although left atrial infusions both reduced aortic pressure and total peripheral resistance, PGE2 always increased heart rate, cardiac output and maximum acceleration. 5 Similar effects were observed with sodium nitroprusside except that it always caused tachycardia and reduced stroke volume. 6 Atropine (0.05 or 1 mg/kg i.v.) reduced or reversed the bradycardia induced by PGI2 but its hypotensive effects were reduced only after 1 mg/kg atropine. After vagotomy changes in cardiac output, stroke volume and maximum acceleration were increased, the hypotensive effects of PGI2 were reduced and the bradycardia was reversed; effects induced by PGE2 were not significantly altered. 7 The hypotension induced by prostacyclin is due to two components, a direct relaxation of vascular smooth muscle and a reflex, non-cholinergic vasodilatation. The bradycardia is reflex in nature and is partially mediated by the vagus pathway.     

Low concentrations of prostaglandin E2 inhibit the prostacyclin-induced elevation of cyclic adenosine 3',5'-monophosphate in elicited populations of rat peritoneal macrophages.

Elevation of cyclic adenosine 3',5'-monophosphate (cyclic AMP) in elicited populations of rat peritoneal macrophages was used as a parameter to examine the influence of prostaglandin E2 (PGE2) on the effects of prostacyclin (PGI2) and (+/-)-5E-13,14-didehydro-carbo-prostacyclin (DDH-carbo-PGI2) in vitro. PGE2, within the range of 1.4 X 10(-9) to 1.2 X 10(-8)M, caused a concentration-dependent inhibition of the rise in cyclic AMP induced by 2.8 X 10(-6) M PGI2 or DDH-carbo-PGI2. With higher concentrations of PGE2 the inhibition was either non-existent or masked by the effect of PGE2 per se on cyclic AMP levels. The present findings suggest that the earlier observed low responsiveness of granuloma macrophages to PGI2, in terms of rise in cyclic AMP, is possibly due to permanent exposure of these cells to environmental endogenous PGE2.     

Conversion of prostacyclin to 6 oxo prostaglandin E1 by rat, rabbit, guinea-pig and human platelets.

The enzymatic catabolism of prostacyclin (PGI2) to 6 oxo prostaglandin E1 (6 oxo PGE1) was studied in platelet-rich and platelet-poor-plasma of rat, rabbit, guinea-pig and man. Rat, rabbit and human platelets convert PGI2 to a product with biological activity and thin layer chromatographic mobility identical to that of authentic 6 oxo PGE1. Platelets from these species also converted 9 beta-[3H]-PGI2 to non-radioactive 6 oxo PGE1 as shown by the progressive loss of extracted radioactivity following incubation. Formation of 6 oxo PGE1 was inhibited by the flavonoid drugs, rutin and naringenin. Guinea-pig platelets did not convert PGI2 to 6 oxo PGE1. Rat, rabbit and guinea-pig platelets do not spontaneously release a 6 oxo PGE1-like substance when incubated at 37 degrees C in the absence of added PGI2 or aggregating agents. The relevance of these findings to the possible physiological and pathophysiological roles of 6 oxo PGE1 in the regulation of platelet function is discussed.     

Formation of 6-keto prostaglandin E1 in mammalian kidneys

1 The metabolism of prostacyclin (PGI2) and 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) was studied in cell-free homogenates of rat, rabbit and guinea-pig kidney. 2 Rabbit kidney converted both PGI2 and 6-keto PGF1 alpha to a stable metabolite with chromatographic and biological activity identical to that of authentic 6-keto PGE1. Activity was found in the kidney cortex but not medulla, was inhibited by NAD+ or NADP+ (5 mM) and showed an optimum temperature requirement of 37 degrees C. 3 Guinea-pig kidney converted PGI2 but not 6-keto PGF1 alpha to a labile, biologically active metabolite which was not 6-keto pge1. 4 No conversion of prostacyclin or 6-keto PGF1 alpha to biologically active metabolites occurred in cell-free homogenates of rat kidney, liver and colon or guinea-pig liver and colon. 5 6-keto PGE1 rapidly lost spasmogenic activity on the rat stomach strip following incubation with rabbit or guinea-pig kidney supernatant in the absence of added cofactors. No loss of activity occurred on incubation with rat kidney. 6 Rutin (50 microM) potently inhibited synthesis of 6-keto PGE1 from added PGI2 by rabbit kidney cortex. This reaction was potentiated by a similar concentration of sulphasalazine, carbenoxolone, imidazole, papaverine or indomethacin. 7 The relevance of these findings for the possible physiological and pathological roles of 6-keto PGE1 in the kidney is discussed.     

Vasodilatation and inhibition of mediator release represent two distinct mechanisms for prostaglandin modulation of acute mast cell-dependent inflammation.

1. Intravital microscopy of the hamster cheek pouch was used to examine the influence of vasodilator prostanoids (prostaglandin E2 (PGE2), PGI2), forskolin, and nitroprusside on the microvascular changes during acute inflammation induced by antigen or histamine. The results extend our previous finding that PGE2 modulates allergic inflammation and histamine release in the cheek pouch model. 2. The microvascular actions of arachidonic acid and different cyclo-oxygenase products (PGE2, PGD2, PGI2, PGF2 alpha, and the thromboxane A2 (TXA2)-analogue U-44069) were first compared with respect to their effects on arteriolar tone. Of the prostaglandins, only PGE2 and PGI2 were potent vasodilators and markedly increased local blood flow. Nitroprusside and forskolin also caused vasodilatation and increased blood flow, but were somewhat less potent than PGE2 and PGI2. 3. Topically applied PGE2 and PGI2 in vasodilator concentrations suppressed the antigen-induced plasma leakage. On the other hand, although the antigen response was predominantly mediated by histamine, both prostaglandins enhanced the plasma leakage evoked by exogenous histamine. 4. In contrast, the vasodilator nitroprusside, in a dose causing an increase in blood flow equal to that of PGE2 and PGI2, potentiated both the histamine-induced plasma leakage, as well as the plasma and leukocyte extravasation after antigen challenge, indicating that the anti-inflammatory actions of the prostaglandins were unrelated to their vasodilator properties per se.(ABSTRACT TRUNCATED AT 250 WORDS)     

Role of pre- and postjunctional inhibition by prostaglandin E2 of lipolysis induced by sympathetic nerve stimulation in dog subcutaneous adipose tissue in situ

1. Canine subcutaneous adipose tissue was isolated and autoperfused in situ after labelling of the noradrenaline stores by (3)H-(-)noradrenaline.2. Prostaglandin E(2) (10-200 ng/ml) increased blood flow and glucose uptake, and caused a dose-dependent inhibition of lipolysis induced by sympathetic nerve stimulation (4 Hz). The actions of exogenous prostaglandin E(2) are therefore similar to those of prostaglandin E(1) in this tissue. There were no consistent effects of prostaglandin E(2) on the vasoconstriction or on the (3)H-noradrenaline overflow induced by nerve stimulation.3. Phenoxybenzamine (1.5-2 mg i.a.) caused a 5-fold increase in (3)H-noradrenaline overflow and a 95% reduction of the vasoconstrictor response to nerve stimulation. The lipolytic response was similar to that of the control. Prostaglandin E(2) (100-200 ng/ml) administered after phenoxybenzamine caused a 90% inhibition of lipolysis, while the vasoconstrictor response was enhanced to about 50% of control. Prostaglandin E(2) inhibited (3)H-noradrenaline overflow by about 50% but it was still larger than that of the control.4. It is suggested that exogenous prostaglandin E(2) inhibits lipolysis induced by sympathetic nerve stimulation mainly by a postjunctional action in canine subcutaneous adipose tissue.     

Interactions between prostaglandin E2 and inhibitors of platelet aggregation which act through cyclic AMP.

Prostaglandin (PG) E2 potentiates platelet aggregation at low concentrations (10(-8)-10(-6) M). It also inhibits aggregation at a higher concentration (10(-5) M), probably by acting through cyclic adenosine 3',5'-monophosphate (cyclic AMP). The mechanism of this biphasic effect of PGE2 and its implications for thrombosis are not clearly understood. Using a sensitive cyclic AMP assay, in conjunction with platelet aggregation studies, we have examined the interactions between PGE2 and other inhibitors of platelet aggregation which act through cyclic AMP. Low concentrations of PGE2 reversed the inhibition of platelet aggregation and increase in cyclic AMP levels induced by PGI2, PGD2 and adenosine (which stimulate adenylate cyclase (AC) through separate and specific platelet receptors). In contrast, low concentrations of PGE2 added to the inhibition of platelet aggregation and increase in cyclic AMP levels induced by forskolin (which stimulates AC directly) and AH-P 719 and DN-9693 (which inhibit cyclic AMP phosphodiesterase (PDE]. These results suggest that the biphasic effect of PGE2 may be mediated by interaction with two separate platelet receptors. Low concentrations appear to potentiate aggregation by acting at a receptor which is directly coupled to an inhibitory guanine nucleotide-binding protein (Gi), possibly the putative PG endoperoxide receptor. High concentrations of PGE2 appear to inhibit aggregation by acting at an additional receptor, probably the PGI2 receptor. The ease with which PGE2 reverses the effects of PGI2, PGD2 and adenosine, but adds to the effects of AH-P 719 and DN-9693, suggests that PDE inhibitors might offer greater potential than these AC stimulators as an anti-thrombotic strategy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Regulation of TNFalpha and interleukin-10 production by prostaglandins I(2) and E(2): studies with prostaglandin receptor-deficient mice and prostaglandin E-receptor subtype-selective synthetic agonists

To know which receptors of prostaglandins are involved in the regulation of TNFalpha and interleukin 10 (IL-10) production, we examined the production of these cytokines in murine peritoneal macrophages stimulated with zymosan. The presence of PGE(2) or the PGI(2) analog carbacyclin in the medium reduced the TNFalpha production to one-half, whereas IL-10 production increased several fold; and indomethacin caused the reverse effects, suggesting that endogenous prostaglandins may have a regulatory effect on the cytokine production. Among prostaglandin E (EP) receptor-selective synthetic agonists, EP2 and EP4 agonists caused down-regulation of the zymosan-induced TNFalpha production, but up-regulation on the IL-10 production; while EP1 and EP3 agonists showed no effect. Macrophages harvested from prostaglandin I (IP) receptor-deficient mice showed the up- and down-regulatory effects on the cytokine production by the EP2 and EP4 agonists or PGE(2), but no effect was obtained by carbacyclin. On the contrary, macrophages from EP2-deficient mice showed the effect by PGE(2), carbacyclin, and the EP4 agonist, but not by the EP2 agonist; and the cells from EP4-deficient mice showed the effect by PGE(2), carbacyclin, and EP2 agonist, but not by the EP4 agonist. These functional effects of prostaglandins well accorded with the mRNA expression of TNFalpha and IL-10 when such expression was examined by the RT-PCR method. The peritoneal macrophages from normal mice expressed IP, EP2, and EP4 receptors, but not EP1 and EP3, when examined by RT-PCR. Thus the results suggest that PGI(2) and PGE(2) generated simultaneously with cytokines by macrophages treated with zymosan may influence the cytokine production through IP, EP2, and EP4 receptors.     

Differential role of microtubules in the control of prostaglandin E2 and beta-adrenergic stimulation of cyclic AMP accumulation in the rat myometrium

A possible modulatory role of microtubules was investigated for the beta-adrenergic and prostaglandin E2 (PGE2)-induced cyclic AMP accumulation in the estrogen-treated rat myometrium. Colchicine, vinblastine and nocodazole, three different antitubulin drugs, enhanced cyclic AMP accumulation caused by PGE2. The effect of inhibitors was dose-(0.1-5 microM) and time-dependent, increased maximal responses without changing EC50 for PGE2, did not occur with trimethyl-colchicinic acid, which does not bind to tubulin, and was totally prevented in tissues pretreated with taxol, an agent that enhances polymerization and stabilization of microtubules. Concomitantly, colchicine reduced the rate and extent of PGE2-induced refractoriness in terms of cyclic AMP. In contrast, the antitubulin drugs failed to affect the rise in cyclic AMP evoked by isoproterenol and cholera toxin but enhanced the response to prostacyclin (PGI2), which is assumed to share common receptors with PGE2. Colchicine and vinblastine also failed to alter the ability of the beta-adrenergic agonist to provoke a cyclic AMP refractory state. Stimulations induced by all effectors were totally insensitive to cytochalasin B. The data suggest a relation between the constraints associated with the microtubules and/or membrane tubulin of the myometrium and the efficacy of PGE2 and PGI2 (but not the beta-adrenergic agonist or cholera toxin) to interact with the cyclic AMP forming system.     

Calcium antagonists stimulate prostaglandin synthesis by cultured rat cardiac myocytes and prevent the effects of hypoxia

The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.     

Stable prostaglandin I1 analog SM-10906 modulates productions of tumor necrosis factor-alpha, interleukin-1 and interleukin-6 in mouse macrophages

The present study investigated the effects of stable agonist for prostaglandin (PG) I2 receptor with PGI1 skeleton, SM-10906, on pro-inflammatory cytokine production by mouse peritoneal macrophages (PEMs) in comparison with PGE1 and PGI2. In mouse PEMs, SM-10906 and PGE1 slightly enhanced interleukin (IL)-6 secretion, but had no effects on tumor necrosis factor-alpha (TNF-alpha) or IL-1 production. SM-10906 concentration-dependently inhibited TNF-alpha, IL-1 and IL-6 releases from lipopolysaccharide-activated mouse PEMs, as with PGE1, PGI2 and cAMP analog. Additionally, SM-10906, PGE1 and PGI2 caused concentration-dependent accumulation of cAMP contents in mouse PEMs. It is concluded that PGI1 analog SM-10906 exerts anti-inflammatory effects on stimulated mouse PEMs by increasing in cAMP levels, as with E-series of PG.     

Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of alpha-methylnoradrenaline on the stimulation-evoked release of 3H-noradrenaline from rat occipital cortex slices

The iminoimidazolidine clonidine reduced concentration-dependently the release of 3H-noradrenaline evoked by electrical stimulation from the rate cerebral cortex. Exposure to the neuronal uptake inhibitors cocaine (10 micro M), desipramine (0.1 to 1 micro M) and amphetamine (1 micro M) significantly increased the stimulation-evoked overflow of tritium. These uptake inhibitors antagonized the effects of clonidine on stimulation evoked 3H-noradrenaline release but failed to modify the inhibition induced by the catecholamine alpha-methylnoradrenaline. Inhibition of monoamine oxidase by preincubation of cerebral cortex slices with 0.5 mM pargyline significantly increased the stimulation-evoked overflow of tritium, but clonidine was as effective as in the controls in inhibiting 3H-noradrenaline overflow. The antagonism by desipramine of the clonidine-induced inhibition of neurotransmission could not be attributed to a blockade of presynaptic alpha-adrenoceptors because: (1) the facilitating effect of phentolamine on 3H-noradrenaline overflow was not modified in the presence of desipramine; (2) the magnitude of the inhibition of the stimulation-evoked 3H-noradrenaline release elicited by alpha-methylnoradrenaline was the same in the presence of cocaine or desipramine; (3) exposure to desipramine in the presence of cocaine did not further increase the stimulation-evoked release of 3H-transmitter. Since the catecholamine alpha-methylnoradrenaline inhibited neurotransmission in the presence of desipramine or cocaine, we can conclude that inhibition of neuronal uptake of noradrenaline antagonized selectively the presynaptic inhibitory effects of imidazolines on alpha 2-adrenoceptors. The influence of the inhibition of neuronal uptake on the presynaptic effects of imidazolines and catecholamines should be taken into account when the relative order of potencies of various alpha 2-adrenoceptors agonists is determined.     

Effects of nerve stimulation and of administration of noradrenaline or potassium chloride upon the release of prostaglandins, I2, E2, and F2 alpha from te perfused mesenteric arterial bed of the rabbit

1 The release of prostaglandin I2 (PGI2), PGE2 and PGF2 alpha from the perfused mesenteric arterial bed of the rabbit was examined at rest, following nerve stimulation and following noradrenaline (NA) or potassium chloride (KCl) administration. 2 Stimulation of adrenergic nerves at 10 Hz caused a significant increase in the release of both PGI2, (assayed in terms of 6-oxo-PGF1 alpha) and PGE2 but a significant decrease in the release of PGF2 alpha. 3 Exogenous Na (2 micrograms) increased the output of PGI2 and PGE2 but left the output of PGF2 alpha unaffected. 4 KCl (15 mg) significantly increased the output of PGF2 alpha but left the output of PGF2 unaffected. 5 It is concluded that PGI2 and PGE2 output from the mesenteric arterial bed of the rabbit increases following stimulation of adrenoceptors. The sympathetic nervous system may therefore modulate PGI2/platelet interaction. 6 Prostaglandins released from the blood vessels by sympathetic nerve stimulation may also modulate adrenergic transmission to the blood vessels.     

Antagonistic properties of RU 24969, a preferential 5-HT1 receptor agonist, at presynaptic alpha 2-adrenoceptors of central and peripheral neurones

The effect of RU 24969 (5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)-1 H-indole) on the electrically evoked 3H overflow was studied in superfused rat brain cortex slices preincubated with 3H-noradrenaline or 3H-serotonin and in superfused segments of the rat vena cava preincubated with 3H-noradrenaline. In cortex slices preincubated with 3H-noradrenaline, RU 24969 facilitated the electrically (3 Hz) evoked 3H overflow. This effect was abolished by phentolamine but was not affected by desipramine or the 5-HT3 receptor antagonist ICS 205-930. The concentration-response curve of noradrenaline for its inhibitory effect on the evoked overflow (determined in the presence of desipramine) was shifted to the right by RU 24969 32 and 100 mumol/l. In this respect, RU 24969 was about 500 times less potent than phentolamine. In cortex slices preincubated with 3H-serotonin, the inhibitory effect of 3.2 mumol/l RU 24969 on the electrically evoked 3H overflow was increased by phentolamine. In segments of the vena cava, RU 24969 inhibited the electrically (0.66 Hz) evoked 3H overflow. The concentration-response curve of RU 24969 was U-shaped, since at concentrations higher than 0.1 mumol/l the extent of inhibition decreased with increasing concentrations of RU 24969. In the presence of phentolamine, the concentration-dependent attenuation of the RU 24969-induced inhibition of overflow was no longer detectable. The present results suggest that RU 24969 is a weak antagonist at presynaptic alpha 2-adrenoceptors (by more than 2.5 log units less potent than as an agonist at presynaptic 5-HT1B auto- and heteroreceptors).     

Effects of prostaglandins E1, E2, F2 alpha and I2 on adrenergic transmission in guinea pig pulmonary arteries

Effects of some prostaglandins (PGs) on adrenergic transmission were studied in guinea pig pulmonary arteries preloaded with 3H-norepinephrine. PGE1 and PGE2 at 0.1 to 100 nM concentration-dependently inhibited 3H-release and contraction evoked at 5 Hz. This inhibition was antagonized by diphloretin phosphate. PGF2 alpha at 1 to 100 nM had no effect on evoked 3H-release and contraction. PGI2 at 1 to 100 nM also failed to modify evoked 3H-release, but markedly and concentration-dependently decreased evoked contraction. There exist presynaptic inhibitory PGE1 and PGE2 receptive sites on adrenergic neurons innervating guinea pig pulmonary arteries, whereas PGF2 alpha and PGI2 produced no effect on the adrenergic neurons.     

Central nervous system effects of arachidonic acid, PGE2, PGF2 alpha, PGD2 and PGI2 on gastric secretion in the rat.

The effects of arachidonic acid, prostaglandin E2 (PGE2), PGF2 alpha, PGD2 and PGI2 on gastric secretion (acid, pepsin and volume) after intracerebroventricular administration were investigated in conscious, pylorus-ligated rats. Arachidonic acid 30-1000 micrograms had no effect on gastric secretion. PGE2 3 and 10 micrograms, reduced gastric secretion as measured 1 hour after injection, although the inhibition induced by 3 micrograms disappeared by 2 h. PGF2 alpha 10 and 30 micrograms, inhibited gastric secretion as measured after 1 h, whereas no change was observed in the gastric contents collected 2 h after 10 micrograms of PGF2 alpha. Intramuscular injection of 30 micrograms of PGF2 alpha had no effect on gastric secretion. Intracerebroventricular administration of 1-30 micrograms of PGD2 or PGI2 had no effect on gastric secretion. The results indicate that PGE2 and PGF2 alpha have a potent central antisecretory action in conscious, pylorus-ligated rats, whereas arachidonic acid, PGD2 and PGI2 do not have any central effects on gastric secretion. It is suggested that PGE2 and PGF2 alpha may be involved in the central nervous system control of gastric secretion.