Evidence for a physiological role of prostaglandins in oviposition by the hen

A single oral dose of indomethacin (25 mg) given 2--4 h before expected oviposition delayed oviposition by about 12 h and suppressed plasma PGE levels by about 90%. Intrauterine injection of PGE-1 (0.2--0.4 microgram/hen) to 12 hens pretreated with 25 mg indomethacin induced oviposition in all birds in about 7 1/2 min. Passive immunization with goat antiserum to PGE-1 delayed oviposition (69%) in 4 hens. It is concluded that prostaglandins play a functional role in oviposition.     

Effects of prostaglandins on the cerebral circulation in the coat

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha) and prostacyclin were also measured. In the dose range tested (0.1-1) microgram/min) PGF2 alpha had no significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI2, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.     

Effects of prostaglandins on the cerebral circulation in the goat

The role of prostaglandins in producing cerebrovasodilation during hypercapnia was tested in goats. Cerebral blood flow (CBF) changes with increasing arterial PCO2 were measured before and after prostaglandin synthesis inhibition with indomethacin or ibuprofen. Both drugs produced significant decreases in CBF under control anesthetized conditions but had no significant effect on the cerebrovascular response to increased arterial PCO2. The effects of direct intracerebrovascular infusion of prostaglandin E₂ (PGE2), prostaglandin F2α (PGF2α) and prostacyclin were also measured. In the dose range tested (0.1–1 ug/min) PGF2α had no significant effect on cerebral blood flow (CBF). Both PGE2 and PGI2 produced an increase in CBF and the increase produced by PGI2 was significantly greater than that produced by PGE2. The effectiveness of each compound in producing cerebrovascular changes is consistent with the endogenous distribution of prostaglandins within the brain. These results suggest that prostaglandins, particularly PGI1, may be important in modulating cerebrovascular tone but have no role in increasing CBF during hypercapnia.     

Effects of indomethacin on intestinal secretion, prostaglandin E and cyclic AMP: Evidence against a role for prostaglandins in cholera toxin-induced secretion

The effects of indomethacin on intestine mucosal cAMP, intestinal fluid secretion, and mucosal and fluid PGE were studied in rabbits in vivo following challenge with cholera toxin. Indomethacin had no effect on cholera toxin-induced fluid secretion or cAMP accumulation. Inhibition of PGE synthesis was achieved by the administration of two but not one injection of indomethacin. These studies provide evidence against a role for PGE in mediating cholera toxin-induced secretion and point out the need to measure prostaglandin levels when using prostaglandin synthetase inhibitors in vivo.     

Evidence for a role of prostaglandins in the antepartum release of relaxin in the pregnant rat

The relationship of the antepartum elevation in serum relaxin levels in pregnant rats to luteolysis was examined by determining the effects of the luteolysin prostaglandin F2 alpha (PGF2 alpha) and the prostaglandin synthetase inhibitor indomethacin on antepartum serum relaxin levels, as well as on luteolysis and birth. Intravenous administration of PGF2 alpha on the morning of Day 20 elevated serum relaxin levels approximately fourfold within 15 min. Administration of the prostaglandin synthetase inhibitor indomethacin from Day 19 until Day 23 protracted luteolysis, delayed or prevented birth, and delayed the antepartum elevation of serum relaxin levels, until after indomethacin treatment had been terminated. Collectively, these results indicate that prostaglandins, in particular PGF2 alpha, may promote the antepartum increase in serum relaxin levels, as well as luteolysis and birth in rats.     

Effects of indomethacin and prostaglandins on ovulation of goldfish

A technique is described whereby elevated temperature and HCG injection yield a high percentage of ovulation in gravid goldfish. Indomethacin (10 μg/g; i.p. injection) completely inhibits ovulation if given within 6 hours following HCG (4 IU/g); the unovulated oocytes develop rapidly into corpora atretica. PGE₁, PGE₂, and PGF_2α (5 μg/g; i.p. injection) induce ovulation in fish treated with indomethacin and HCG; PGE₂ was most effective when given 11 hours after HCG. The results suggest that the ovulatory action of prostaglandins following HCG stimulation is at the level of the ovary and that it is restricted to a period between 7 and 12 hours after the gonadotropin injection.     

Effects of indomethacin and prostaglandins on ovulation of goldfish.

A technique is described whereby elevated temperature and HCG injection yield a high percentage of ovulation in gravid goldfish. Indomethacin (10 mug/g; i.p. injection) completely inhibits ovulation if given within 6 hours following HCG (4 IU/g); the unovulated oocytes develop rapidly into corpora atretica. PGE1, PGE2, and PGF2alpha (5 mug/g; i.p. injection) induce ovulation in fish treated with indomethacin and HCG; PGE2 was most effective when given 11 hours after HCG. The results suggest that the ovulatory action of prostaglandins following HCG stimulation is at the level of the ovary and that it is restricted to a period between 7 and 12 hours after the gonadotropin injection.     

Effects of indomethacin on intestinal secretion, prostaglandin E and cyclic AMP: evidence against a role for prostaglandins in cholera toxin-induced secretion.

The effects of indomethacin on intestine mucosal cAMP, intestinal fluid secretion, and mucosal and fluid PGE were studied in rabbits in vivo following challenge with cholera toxin. Indomethacin had no effect on cholera toxin-induced fluid secretion or cAMP accumulation. Inhibition of PGE synthesis was achieved by the administration of two but not one injection of indomethacin. These studies provide evidence against a role for PGE in mediating cholera toxin-induced secretion and point out the need to measure prostaglandin levels when using prostaglandin synthetase inhibitors in vivo.     

Effects of indomethacin and prostaglandins on the spawning behaviour of female goldfish

In goldfish, injection of ovulated eggs (from donor females) through the ovipore and into the ovarian lumen of females with vitellogenic oocytes induces spawning behaviour within several hours. Intraperitoneal (i.p.) injection of indomethacin (IM), 10 μg/g, either 10 h prior to, or coincident with, injection of ovulated eggs, completely inhibits the onset of spawning behaviour. IM injection similarly terminates ongoing spawning behaviour induced by egg injection. PGF_2α (5 μg/g; i.p. injection) restores spawning behaviour of egg-injected, IM-blocked fish; at the same dosage, PGE₂ is marginally effective and PGE₁ is without effect. As PGF_2α and PGE₂ also induce spawning behaviour in females which have not been injected with ovulated eggs, it is suggested that distension of the oviduct following ovulation or egg injection results in the release of PG which then acts in some way to induce spawning behaviour. The ability of PG to induce spawning behaviour is eliminated by hypophysectomy and restored by treatment with salmon gonadotropin: no steroid treatment was effective in restoring PG-induced spawning in fish which had been hypophysectomized for 3–4 months. The possible mode of action of PG in inducing spawning behaviour in female goldfish is discussed.     

Effect of indomethacin on atropine-resistant transmission in rabbit and monkey urinary bladder : Evidence for involvement of prostaglandins in transmission

The effects of 2.9 × 10⁻⁵M atropine and 2.8 × 10⁻⁶M indomethacin on responses of rabbit and monkey detrusor muscle to transmural stimulation were investigated. Responses to transmural stimulation were partially inhibited by atropine. Indomethacin caused further inhibition in the presence of atropine, but did not alter responses to acetylcholine. Prostaglandins E₂ and F_2α contracted rabbit and monkey detrusor. It is suggested that prostaglandins are liberated during stimulation of excitatory nerves to the rabbit and monkey detrusor, and contibute to the resultant contractile response.     

Evidence for a role of prostaglandins in atropine-resistant transmission in the mammalian urinary bladder

It has been known for many years that atropine and other anti-cholinergic drugs readily inhibit the contractile responses of the detrusor portion of the mammalian urinary bladder to exogenous acetylcholine, but only partially inhibit responses to nerve or transmural stimulation (1,2). These findings suggest that the excitatory innervation to the bladder consists not only of cholinergic nerves but also of non-cholinergic nerves. The possibility that such a second excitatory transmitter could be a catecholamine, 5-hydroxytryptamine, bradykinin or histamine has not been supported by experimentation (2). Burnstock, Dumsday and Smythe (3) have presented evidence that ATP might be the second transmitter in the bladder. In the present study we are investigating the role, if any, of prostaglandins in the non-cholinergic responses of urinary bladder to transmural stimulation. For this purpose, we have studied the effects of indomethacin, an inhibitor of prostaglandin synthesis, on responses to transmural stimulation.     

Evidence for a role of high Km aldehyde reductase in the degradation of endogenous gamma-hydroxybutyrate from rat brain

gamma-Hydroxybutyrate (GHB) is a putative neurotransmitter in brain. We have already demonstrated that it is transformed into gamma-aminobutyrate (GABA) by rat brain slices incubated under physiological conditions. This conversion occurs via a GABA-transaminase reaction. Therefore, succinic semialdehyde, the oxidative derivative of GHB, appears to be the primary catabolite of GHB degradation. Apparently, the kinetic characteristics and pH optimum of GHB dehydrogenase (high Km aldehyde reductase) in vitro do not favor a role for this enzyme in endogenous brain GHB oxidation. However, in the presence of glucuronate, glutamate, NADP and pyridoxal phosphate, pure GHB dehydrogenase, coupled to purified GABA-transaminase does produce GABA from GHB at an optimum pH close to the physiological value and with a low Km for GHB.     

Prevention by aluminium phosphate of gastric lesions induced by ethanol in the rat: role of endogenous prostaglandins and sulfhydryls

This study was designed to demonstrate the cytoprotective effect of an antacid containing aluminium phosphate (Phosphalugel) against ethanol-induced gastric injury in the rat and to determine whether this cytoprotective effect is mediated by endogenous prostaglandins and sulfhydryls. We have quantitatively evaluated gastric mucosal lesions using macroscopic and histological techniques one hour after ethanol administration. Two ml of aluminium phosphate given orally one hour before administration of 2 ml of 100% ethanol significantly (p less than 0.01) reduced the area of macroscopic lesions induced by ethanol (3.3 +/- 0.9%) when compared to distilled water (20 +/- 4.8%). The histological study showed that aluminium phosphate prevented deep tissue necrosis. However, it did not protect surface epithelial cells against ethanol injury. Pretreatment with indomethacin, 5 mg/kg sc one hour before aluminium phosphate, slightly but significantly (p less than 0.05) reduced the cytoprotective effect of aluminium phosphate. Macroscopic lesions occupied 4.3 +/- 0.94% and 1.88 +/- 0.41% of total mucosal area in indomethacin group and in vehicle group, respectively. On the other hand, the sulfhydryl blocker, N-ethyl-maleimide, 10 mg/kg sc, given one hour before aluminium phosphate, completely abolished the cytoprotective effect of aluminium phosphate (32.92 +/- 4.85% in N-ethyl-maleimide group versus 3.78 +/- 1.41% in vehicle group; p less than 0.01). These results show that aluminium phosphate has a cytoprotective effect against ethanol injury in the rat. This property appears to be mediated by both endogenous prostaglandins and sulfhydryls.