CRF: an inhibitor of neurogenic plasma extravasation produced by saphenous nerve stimulation.
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Animals↗
Biomedical subjects
E T Wei
Publications and source records attributed to E T Wei.
Neurotoxic esterase in rooster testis.
Neurotoxic esterase (NTE) is the putative target protein in the nervous system for the initiation of organophosphorus-induced delayed neuropathy. Here it is reported that NTE activity is present in rooster testis. Complete titration of rooster testis phenyl valerate esterases with paraoxon shows that about 15% of the enzymic activity is resistant to paraoxon. NTE activity after complete mipafox titration accounts for 30% of paraoxon-resistant phenyl valerate esterases and corresponds to 7.93 +/- 0.39 nmol/min/mg of protein (mean +/- SD, n = 7). Testis NTE is inhibited in vitro similarly to brain NTE by several organophosphorus compounds. Subcellular fractionation studies of the testis indicate that most NTE activity is particle bound. Testis NTE is also inhibited in vivo by several organophosphorus esters but to a lesser extent than brain NTE. Birds doses with organophosphorus compounds, causing delayed neuropathy, became grossly ataxic, but no testicular pathology was noted by light microscopy in roosters killed 15 days after administration. Serum testosterone levels also measured 15 days after dosing were not different from those of a control group. Recovery of NTE activity was faster in testis than in brain (4 days vs 6 days to recover to 50% of initial activity) in animals that received a high dose of an organophosphorus ester which cause delayed neuropathy.
Animals↗
Depressor and natriuretic activities of several atrial peptides.
Mammalian atria contain peptides that have depressor and natriuretic activities. Four peptides, atriopeptin I to III (AP I to III) and alpha-human atrial natriuretic factor (alpha-hANP), were synthesized and assayed in the urethane-anesthetized rat for cardiovascular changes and natriuretic activities. All four peptides produced depressor responses and natriuresis. The relative activities were: alpha-hANP = AP III greater than AP II greater than AP I. The disappearance of iodinated AP III from plasma was rapid, with an estimated half-life of 2.5 min. Atriopeptin III was degraded by tissue homogenates, the relative activities being: kidney greater than liver greater than lung greater than plasma greater than heart. The HPLC profile of AP III suggested that smaller peptide fragments were formed after incubation with kidney homogenates. The degradation of AP III was inhibited by bestatin, an aminopeptidase inhibitor, and SQ 20881, a carboxypeptidase inhibitor.
Animals↗
Peripheral opioid receptors influencing heart rate in rats: evidence for endogenous tolerance.
Opioid peptides injected into the circulation of rats evoke a vagally mediated bradycardia. The intravenous ED50 of morphine for producing a greater than or equal to 10% fall in heart rate was determined in urethane-anesthetized rats. Hypophysectomy, or adrenalectomy plus treatment with dexamethasone (0.5 microgram/h, s.c., 1 day), procedures that remove endogenous sources of opioid peptides, increased the sensitivity of the animal to morphine bradycardia by 6-10-fold. Conversely, stressing the animals by exposure to cold (4-6 degrees C for two days) elevated the ED50 for morphine sulfate and for beta h-endorphin by about 5-fold. Dexamethasone infusions prevented the cold-induced desensitization to morphine. Intravenous administration of rat corticotropin-releasing factor (CRF) also desensitized the animals to morphine. CRF alone produced a fall in blood pressure and heart rate. The bradycardia was prevented by pretreatment with naloxone. These results indicate that the sensitivity of vagal opioid chemoreceptors is influenced by endogenous sources of opioid peptides. This phenomenon can be called 'endogenous tolerance'.
Adrenalectomy↗
Mechanisms underlying the pressor responses to acute and chronic intraventricular administration of carbachol in the rat.
Infusions of carbachol into the posterior region of the 3rd ventricle of rats for 7 days produced a sustained elevation of blood pressure and heart rate at doses of 0.6 and 1.2 microgram/hr, but only transient rises in blood pressure were obtained at 2.4 microgram/hr. Carbachol, at 0.6 microgram/hr, increased water consumption. At 1.2 microgram/hr, the dipsogenic effect was observed in 50% of the animals and at 2.4 microgram/hr there was no significant change in drinking. Plasma vasopressin levels, measured by radioimmunoassay, were increased by 19-fold 3 min after acute i.c.v. administration of carbachol (0.5 microgram/rat). However, in rats infused with carbachol for 2 or 5 days, the vasopressin levels were not significantly different from controls. The pressor responses to acute and chronic administration of carbachol could be ascribed to the stimulation of periventricular muscarinic receptors because the effects were blocked by atropine, but not by hexamethonium. In carbachol-infused animals, the pressor responsiveness to i.v. norepinephrine and vasopressin were unchanged. From studies using phentolamine, chlorisondamine and a specific vasopressin vasopressor antagonist, it could be inferred that the pressor responses to acute i.c.v. injections of carbachol were due to increased sympathetic activity and vasopressin release. However, the sustained hypertension produced by chronic infusion of carbachol was due primarily to increased sympathetic activity and not to increased plasma levels of vasopressin.
Animals↗
Sensitivity to morphine-evoked bradycardia in rats is modified by dynorphin (1-13), Leu- and Met-enkephalin.
Intravenous injection of morphine evokes, in the rat, a vagal chemoreflex resulting in bradycardia, hypotension and transient apnea. The morphine ED50 for producing bradycardia was utilized here as an index of the sensitivity to opioid stimulation of the organism. The potency of morphine for producing bradycardia can be modified by dynorphin (1-13), Leu- and Met-enkephalin. Both dynorphin (1-13) and Leu-enkephalin administered s.c. to normal and morphine-tolerant rats, 30 min before blood vessel cannulation and testing, lowered the morphine ED50 for bradycardia. Dynorphin (1-13) was 3 times more potent than Leu-enkephalin. Under the same test conditions, Met-enkephalin, given s.c. (0.45-0.9 mumol/kg) 30 min before morphine challenge, produced only desensitization to morphine-evoked bradycardia. The effects of dynorphin (1-13) were biphasic with respect to time of injection. When dynorphin (1-13) (0.3 mumol/kg s.c.) was injected s.c. 2 hr before morphine challenge, animals were desensitized to morphine by 2.5 times. Dynorphin (1-13) (0.19-0.77 nmol/hr s.c.) co-infused with morphine (74 nmol/hr s.c.) for 2 days accelerated tolerance development to morphine bradycardia. These results confirm previous studies which suggest that opioid peptides having Leu- or Met-enkephalin at its N-terminus manifest different pharmacological properties in vivo.
Analgesics↗
Inhibition of shaking movements in rats by central administration of cholinergic and adrenergic agents.
Shaking movements of the body, similar to that made by a dog when wet ('wet-dog shakes'), occur in rats in response to pharmacological stimuli and in response to stimuli associated with cold and skin irritation. In this study, shaking movements, elicited by a variety of stimuli, were inhibited by central administration of nanomolar doses of drugs that act as agonists on muscarinic, adrenergic, and opiate receptors. The brain regions that mediate the drug inhibition of shaking appear to be located in the medial preoptic area and in structures lining the aqueduct and fourth ventricle.
Animals↗
Inhibition of an opioid-evoked vagal reflex in rats by naloxone, SMS 201-995 and ICI 154, 129.
Intravenous injection of opioid agonists in rats evokes a vagal reflex resulting in a fall in heart rate, and blood pressure. Three opioid antagonists, naloxone, SMS 201-995, and ICI 154,129 were used to assess the nature of the opioid receptors that mediate the vagal reflex. The agonists used were morphine, Tyr-Pro-NMePhe-D-Pro-NH2 (PLO17), and D-Ala2-Leu5-enkephalin (DADL). At challenge doses of morphine, PLO17, and DADL at five times the ED50 for bradycardia, the naloxone ED50 for DADL was nine times greater than that for morphine and PLO17. The pA2 value of naloxone against DADL was significantly less than that for morphine and PLO17. The antagonist properties of SMS 201-995 were similar to those of naloxone. ICI 154,129, a putative delta receptor antagonist, was not, however, selective in its antagonism of opioid bradycardia. Both SMS 201-995 and ICI 154,129, when injected alone, produced changes in heart rate and blood pressure. The cardiovascular actions of the peptide antagonists were not affected by naloxone hydrochloride at doses up to 4 mg/kg i.v.
Animals↗
AG-3-5: a chemical producing sensations of cold.
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Animals↗
Nitroaromatic carcinogens in diesel soot: a review of laboratory findings.
The automobile industry plans to increase production of diesel-powered passenger cars because diesel engines provide better fuel economy than conventional gasoline engines. Diesel engines, however, produce more soot, and increased use of diesel cars will result in more discharge of diesel soot into the atmosphere. Recently, a new class of chemicals, called nitroaromatic compounds, have been identified in chemical extracts of diesel soot. Some of these nitroaromatic compounds produce mutations when tested in in vitro bacterial and mammalian cell assays, and cancer when tested in animals. Here, we review the relevance of these new laboratory findings to current deliberations over emission standards for particles from diesel cars.
Carbon↗
An etorphine-evoked vagal reflex in rats is inhibited by naloxone, N-methylnaloxone, and SMS 201-995.
Intravenous injection of opiates in rats is known to produce a rapid fall in heart rate, blood pressure, and respiratory frequency. Etorphine, a potent opiate agonist which reaches central and peripheral receptors, administered at 1.1 nmol/kg i.v., evoked these characteristic effects in the urethane-anaesthetized rat. Three opiate antagonists, with somewhat different properties, have been used to assess the site of action of etorphine-induced bradycardia, hypotension, and inhibition of respiration. The antagonists used were naloxone hydrochloride, N-methylnaloxone bromide, and SMS 201-995. Low doses of naloxone blocked the cardiovascular and respiratory effects of etorphine. N-Methylnaloxone blocked the bradycardia, hypotension and the initial phase of apnea produced by etorphine but not the subsequent slowing of respiration. SMS 201-995 blocked the bradycardia and partially antagonized the hypotension and inhibition of respiratory rate produced by etorphine. These results indicate that N-methylnaloxone and SMS 201-995 can block the peripheral receptors which mediate opiate-induced bradycardia. Naloxone blocks both the central and peripheral actions of etorphine and so more completely antagonizes the cardiovascular and respiratory effects of etorphine.
Animals↗
Potent morphiceptin analogs: structure activity relationships and morphine-like activities.
Morphiceptin (Tyr-Pro-Phe-Pro-NH2), a nonenkephalin peptide, is an opioid agonist highly selective for mu opiate receptors. Chemical modification of Tyr-Pro-Phe-Pro-NH2 was carried out by substituting structurally related amino acids at residues 2, 3 and 4. The morphiceptin analogs synthesized were then examined for receptor binding activities using 125I-labeled FK 33,824 (Tyr-D-Ala-Gly-NMePhe-Met(O)-ol) as the mu-ligand and 125I-labeled D-Ala2,D-Leu5-enkephalin as the delta-ligand, and for inhibitory activities on electrically evoked smooth muscle contraction of mouse vas deferens and isolated myenteric plexus-longitudinal muscle strips of guinea-pig ileum. All of these analogs showed virtually no activity at delta opiate receptor binding sites. Methylation of the nitrogen atom of phenylalanine and the substitution at the C-terminal of L-proline by D-proline produced potent mu-agonists, the prototype analog being Tyr-Pro-NMePhe-D-Pro-NH2 (PL017). The IC50 values of morphiceptin and its analogs for mu receptor binding were correlated to the ED50 values in the guinea-pig ileum assay, suggesting that the ileum effects were mediated by mu receptor interactions. A similar correlation between mu receptor binding activity and the ED50 values in the mouse vas deferens assay suggested that morphiceptin and its analogs also acted on mu receptors in this tissue. This idea is supported by the observation that naloxone has a high pA2 value of 8.71 against PL017 in mouse vas deferens. In in vivo studies, PL017 administered centrally into the rostral portion of the 4th ventricle produced long-lasting, naloxone-reversible analgesia in rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Tolerance to morphine bradycardia in the rat.
Intravenous injection of opiate agonists produces in the rat a precipitous but transient fall in heart rate. This bradycardia, which may be a vagal chemoreflex, appears to originate from peripheral opiate receptors because the onset is faster after injections of morphine into the peripheral circulation than after central injections. The bradycardia is blocked by i.v. administration of tertiary and quaternary naloxone at doses which are not effective centrally. Tolerance develops to morphine bradycardia after s.c. infusions of morphine sulfate (e.g., 74 nmol/hr/rat s.c. for 2 days elevated the morphine ED50 by 22 times), but not after central infusions of morphine at doses which are sufficient to produce physical dependence and tolerance to morphine analgesia. Subcutaneously infused morphine animals are cross-tolerant to FK33,824 (Tyr-D-Ala-Gly-NMePhe-Met(O)-ol), a potent enkephalin analog, and vice versa, but are not tolerant to serotonin or phenyldiguanide. Vagal bradycardia may be a convenient index for studying the peripheral action of opioid agonists.
Animals↗
Blood pressure elevation in rats by peripheral administration of Tyr-Gly-Gly-Phe-Met-Arg-Phe and the invertebrate neuropeptide, Phe-Met-Arg-Phe-NH2.
Phe-Met-Arg-Phe-NH2 (FMRFamide), injected at less than 1 mumol/kg intravenously in the anesthetized rat, produces sharp elevations of blood pressure and changes in respiration. The effects were dependent on the carboxyterminal Arg-Phe (RF) configuration and were stereospecific for these two amino acids. A related peptide with RF carboxyterminus, gamma 1-melanotropic stimulating hormone, also had potent blood pressure stimulating activity. The mechanisms underlying the pressor effect of FMRFamide have not yet been established but this pressor action was not significantly attenuated by standard pharmacologic antagonists or prevented by removal of the adrenal or pituitary gland.
Animals↗
MIF-like sequences in milk and wheat proteins.
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Amino Acid Sequence↗
Evidence for enzymatic reduction of 1-nitropyrene by rat liver fractions.
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Animals↗
Infusions of chemicals into the brain and the development of sustained elevations of blood pressure in the rat.
Osmotic minipumps were used to infuse carbachol chloride (1.23 micrograms/hr), echothiophate iodide (0.5 microgram/hr), histamine dihydrochloride (10 micrograms/hr), prostaglandin E2 (1.0 microgram/hr) and thyrotropin-releasing hormone (0.5 and 5.0 micrograms/hr) solutions into the cerebral ventricles of unanesthetized rats and blood pressure was measured by the tail-cuff method. Histamine dihydrochloride, prostaglandin E2 and thyrotropin-releasing hormone produced an initial rise in blood pressure, but were not effective in producing sustained elevations in blood pressure. Carbachol infusions elevated blood pressure throughout the 7-day infusion period when results were compared to saline-infused animals. Infusions of echothiophate iodide, an anticholinesterase agent, produced an initial rise in blood pressure but these pressor effects were not sustained. In animals infused with echothiophate for 7 days, the pressor response to a challenge dose of echothiophate was diminished.
Animals↗
Analgesic activity of intracerebroventricular administration of morphiceptin and beta-casomorphins: correlation with the morphine (micro) receptor binding affinity.
Analgesic activities of morphiceptin, beta-casomorphins, [D-Ala2, D-Leu5]enkephalin and Sandoz peptide, FK 33-824, were examined by intracerebroventricular administration in rats. Their relative potencies in vivo were compared with their receptors binding activities. The receptors binding affinities were determined from the competition curves against [3H]naloxone binding in the absence and presence of sodium ions for morphine (micro) receptors and against 125I-[D-A1A2, D-Leu]enkephalin binding for enkephalin (delta) receptors. A good correlation between analgesic activity and morphine (micro) receptor but not enkephalin (delta) receptor binding affinity was obtained. These data extend the hypothesis that morphine (micro) receptors mediate the major portion of the analgesic activity of opioids.
Analgesia↗