Opioid properties of beta-lipotropin fragment 60-65, H-Arg-Try-Gly-Gly-Phe-Met-OH.
Explore the source record for details and available documents.
Analgesia↗
Biomedical subjects
E T Wei
Publications and source records attributed to E T Wei.
Surface charge and hemolytic activity of asbestos.
Explore the source record for details and available documents.
Adsorption↗
Chemical stimulants of shaking behaviour.
Explore the source record for details and available documents.
Animals↗
Effects of clonidine on morphine withdrawal signs in the rat.
The influence of clonidine on the naloxone-induced withdrawal signs, escape attempts and precipitated shakes, was studied in morphine-dependent rats. Clonidine injected i.p. or intraventricularly (i. vent.) inhibited precipitated shakes and potentiated escape attempts induced by naloxone in morphine-dependent rats. Under pentobarbital anesthesia, precipitated shakes and ice water-induced wet shakes were inhibited by clonidine and norepinephrine. Clonidine injected i. vent. reduced body temperatures in morphine-dependent rats but not in placebo pellet-implanted rats. We suggest that clonidine modulates morphine withdrawal signs by potentiating the behavior associated with heat dissipation (escape attempts) and inhibiting the behavior associated with heat gain mechanisms (precipitated shakes). These effects may occur via stimulation of central noradrenergic mechanisms.
Anesthesia↗
Pro-Leu-Gly-NH2 and pareptide inhibit development of tolerance to haloperidol catalepsy in the mouse.
Single doses of MIF-1 (0.03-2.0 mg/kg, SC) and chronic pretreatments with MIF-1 (0.03-2.0 mg/kg, SC, BID, 3 1/2 days) or pareptide (0.25 mg/kg, SC, BID, 3 1/2 days) did not affect the acute cataleptic response to haloperidol in the mouse. Chronic pretreatment with haloperidol (8.0 mg/kg, IP, BID, 3 days) decreased the duration of catalepsy in mice given smaller challenge dose of haloperidol (2.0 or 3.0 mg/kg, IP) 15 hours after the last pretreatment injections. Administration of either MIF-1 or pareptide to mice also chronically pretreated with haloperidol antagonized the development of tolerance.
Animals↗
CRF-evoked bradycardia in urethane-anesthetized rats is blocked by naloxone.
CRF, injected IV at a dose of 6 nmol/kg, produced a fall in blood pressure and in heart rate in urethane-anesthetized rats. The CRF-bradycardia was not obtained in hypophysectomized animals, in animals pretreated with dexamethasone, or in animals pretreated with the narcotic antagonist, naloxone (1 mg/kg, IV). By contrast, the hypotensive effects of CRF were not affected by these procedures. Vagotomy or pretreatment with a low dose of N-methylnaloxone did not affect the CRF-bradycardia, indicating that the slowing of the heart was not due to parasympathetic stimulation or due to a peripherally mediated opioid chemoreflex. The results suggested that the CRF-bradycardia was mediated by the release of opioid peptides from the pituitary.
Animals↗
Pharmacological activities of the MIF-1 analogues Pro-Leu-Gly, Tyr-Pro-Leu-Gly and pareptide.
The pharmacological activities of the related free acid analogues of MIF-1, Pro-Leu-Gly (PLG) and Tyr-Pro-Leu-Gly (YPLG), were investigated because of the possibility that they may be formed during the digestion of milk and wheat proteins in vivo. The amino acid sequences -Tyr-Pro-Leu-Gly- and -Pro-Leu-Gly- are present in proteins from these foods. Chronic administration of either PLG (0.25 mg/kg, SC, BID) or the control substance, pareptide (0.25 mg/kg, SC, BID), antagonized the development of tolerance to the cataleptic effects of haloperidol in mice. The effect of YPLG (0.25 mg/kg, SC, BID) on the development of this tolerance was borderline and not statistically significant. Nanomolar concentrations of PLG, YPLG, and pareptide each increased the in vitro binding of 3H-apomorphine to rat striatal receptors. In this in vitro system, bell-shaped dose response curves were observed for each peptide. The effects of these peptides on tolerance development and apomorphine binding are similar to those previously reported for MIF-1 and demonstrate that amidation at the carboxyl terminus is not required for biological activity.
Animals↗
Corticotropin-releasing factor inhibition of substance P-induced vascular leakage in rats: possible sites of action.
Substance P (SP), 40 micrograms/kg SC, induced protein leakage in the skin, muscle, trachea and esophagus of the anesthetized rat as measured by Monastral blue B labeling of small blood vessels. CRF, 30 micrograms/kg SC, injected 30 min before SP, decreased the SP-induced dye leakage. To locate where CRF might act, autoradiographic studies of [125I]-CRF binding to esophageal segments were conducted and displaceable binding of [125I]-CRF to submucosal elements in the esophageal epithelium were revealed, suggesting that CRF acts on selective sites to reduce vascular leakage.
Animals↗
Potent mutagenic impurities in a commercial sample of 3-nitro-9-fluorenone.
A commercial sample of 3-nitro-9-fluorenone was a potent mutagen in the Ames Salmonella assay, producing 1000 TA98 net revertants per plate at 0.76 microgram/plate without the presence of liver homogenates (-S9). After purification by high-pressure liquid chromatography (HPLC), 3-nitro-9-fluorenone was found to be at least 6 times less active than the parent sample. The commercial sample was fractionated by HPLC and the mutagenic impurity peaks collected and subjected to high-resolution mass spectrometry (HRMS). The mass spectra of 2 potent mutagenic fractions showed the principal molecular species to be a dinitrofluorenone and an acetamidomononitrofluorenone. Samples of synthetic 2,7-dinitro-9-fluorenone and 2-acetamido-3-nitro-9-fluorenone had mutagenic activities, HPLC retention times, and mass spectra characteristics similar to the mutagenic impurity fractions collected from the commercial sample.
Chromatography, High Pressure Liquid↗
Epinephrine-induced pulmonary oedema in rats is inhibited by corticotropin-releasing factor.
In various animal models of injury to skin, mucous membranes, muscle and brain, corticotropin-releasing factor (CRF) attenuated vascular leakage in the injured tissues. Here, the effects of CRF on a rat model of pulmonary oedema were examined. Male albino rats (220-290 g) received saline or CRF s.c., 30 min before pentobarbital anaesthesia, 60 mg/kg i.p., and 1 h before 1-epinephrine bitartrate (Epi), 30 micrograms/kg i.v. Within 30 min after Epi all (n = 27) saline-pretreated rats were dead from pulmonary oedema, but animals receiving human/rat CRF at doses of 7 to 57 micrograms/kg s.c. (n = 25) were all alive. Body wt, wet and dry wt of lungs were used to calculate an oedema index. This index increased from 3.6 +/- 0.1 to 9.6 +/- 0.3 after Epi but was inhibited by 87% after CRF 28 micrograms/kg s.c. The ED50 of CRF for reducing pulmonary oedema was 3.2 (1.3-7.4) micrograms/kg s.c. Mean arterial pressure increased from 119 +/- 4 to 167 +/- 2 mmHg after Epi 10 micrograms/kg i.v., but was not different (118 +/- 3 to 169 +/- 4 mmHg) after CRF pretreatment, 6 micrograms/kg s.c., a dose which reduced lung oedema. Pharmacokinetic estimates suggest that plasma levels of CRF sufficient to attenuate lung oedema in rats approximate those seen in pregnant women at delivery, raising the possibility that endogenous CRF may protect the maternal organism during parturition.
Animals↗
Adverse health effects of selenium in humans.
Epidemiologic studies and case reports have shown that chronic exposure to selenium compounds is associated with several adverse health effects in humans. An early toxic effect of selenium is on endocrine function, particularly on the synthesis of thyroid hormones following dietary exposure of around 300 micrograms Se/d, and on the metabolism of growth hormone and insulin-like growth factor-1. Other adverse effects of selenium exposure can be the impairment of natural killer cells activity and at higher levels, hepatotoxicity and gastrointestinal disturbances. Dermatologic effects, such as nail and hair loss and dermatitis, occur after exposure to high levels of environmental selenium. Assessing the toxicity and morbidity after long-term exposure to environmental selenium is difficult: neurotoxicity, particularly the degeneration of motor neurons leading to increased risk of amyotrophic lateral sclerosis, might occur after chronic exposure to both organic and inorganic selenium compounds. The results of laboratory investigations and cohort studies suggest that selenium species exhibit a bivalent effect in cancer, either increasing or decreasing risk. Current environmental selenium exposure limits appear to be inadequate for averting adverse health effects.
Biomarkers↗
Inhibition of mouse melanoma cell proliferation by corticotropin-releasing hormone and its analogs.
BACKGROUND: Observations that epidermal cells release both corticotropin-releasing hormone (CRH) and proopiome lanocortin (POMC) peptides has raised questions about the physiological relevance of this hypothalamo-pituitary-like system in mammalian skin. As CRH has shown anti-proliferative effects on cultured keratinocytes, we tested whether CRH can also regulate growth of melanoma cells. MATERIALS AND METHODS: CRH, [D-Glu20]-CRH, [D-Pro5]-CRH, acetyl-cyclo(30-33)[D-Phe12,D-Glu20,Nle21,D-His32,Lys33,D-Nle38]-CRH(4-41), acetyl-cyclo(30-33)[D-Phe12,Nle18,D-Glu20,Nle21,D-Ala32]-urotensin I(4-41), urocortin, and sauvagine were tested on Cloudman melanoma cell proliferation in culture and B16 melanoma tumor growth in C57B1/6 mice. Calcium-sensitive fluorescence measurements were used to examine the effect of CRH on intracellular Ca2+ signaling. The effects of CRH and [D-Glu20]-CRH on blood pressure were compared by measuring mean arterial pressure in anesthetized rats. RESULTS: CRH and six analogs were tested, and all demonstrated exceptional potency in inhibiting Cloudman cell proliferation in culture, with half-maximal effective concentrations ranging between 0.2 and 100 pM. The amplitude of ionomycin-induced Ca2+ influx into Cloudman cells grown in suspension was reduced by 50% after 48-hr exposure to CRH. Daily injections of CRH or [D-Glu20]-CRH, 100 micrograms/kg.day s.c., for 5 days, reduced net B16 tumor volume in mice by 30-60% compared to control animals. [D-Glu20]-CRH was less hypotensive compared to CRH, despite having similar anti-proliferative potency. CONCLUSION: CRH, and various analogs thereof, inhibit proliferation of Cloudman cells in culture, and inhibit B16 tumor growth rate in vivo, most likely by activation of endogenous CRH1 receptors and subsequent altered intracellular Ca2+ signaling. CRH analogs, such as [D-Glu20]-CRH, with less hypotensive activity may provide new directions of therapy for melanoma.
Amino Acid Substitution↗