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E T Wei

Publications and source records attributed to E T Wei.

At least 37 records · Page 2Linked to original sources
PubMed1993

Peripheral anti-inflammatory actions of corticotropin-releasing factor.

Swelling, oedema, and loss of fluids and protein from the vascular compartment are immediate responses seen in living tissues after severe injury. Peptides of the corticotropin-releasing factor (CRF) superfamily have the unusual property of preventing the vascular leakage that occurs in tissues after damage. For example, CRF decreased protein extravasation, oedema and swelling in the anaesthetized rat's paw after exposure to heat or to extreme cold, in tracheal mucosa after exposure to formaldehyde, in skeletal muscle after a knife cut, and in brain cortex after freezing. The anti-inflammatory actions of CRF were independent of steroid release or hypotensive effects. CRF was a functional antagonist of inflammatory mediators such as histamine and substance P. It inhibited neurogenic inflammation, but interactions with unmyelinated sensory neurons did not account for the wide range of CRF's anti-inflammatory activities. Localized application of CRF prevented histamine-induced leaks in the hamster cheek pouch, and displaceable binding sites to iodinated CRF were found on blood vessels and on epithelial cells in close proximity to sites of vascular leakage. These results indicated peripheral sites of action. CRF may be the first example of a peptide hormone demonstrated to have potent anti-inflammatory agonist actions in vivo.

Animals↗
PubMed1993

Novel anti-inflammatory undecapeptides that contain anisolyated glutamic acid derivatives.

In various animal models of tissue injury, corticotropin-releasing factor (CRF) and related peptides inhibit swelling, edema and loss of protein from the vascular compartment. To search for smaller peptide segments of CRF that might retain anti-inflammatory activity, the authors tested peptides similar to the carboxy terminals of ovine (o) and human/rat (h/r) CRF. Also, because h/rCRF(35-39), -Arg-Lys-Leu-Met-Glu-, resembles Arg-Lys-Leu-Leu-Glu-, a sequence found in many intermediate filament proteins, analogous peptides were evaluated. Ovine CRF(21-41), -Met-Thr-Lys-Ala-Asp-Gln-Leu-Ala-Gln-Gln-Ala-His-Ser-Asn-Arg-Lys- Leu-Asp-Ile-Ala-NH2, its carboxy terminal carboxyl derivative, oCRF(21-41)-OH, and the fragments, oCRF(26-41) and oCRF(30-41), were inactive when assayed at 5 mg/kg i.v. on edema induced in the pentobarbital-anesthetized rat's hindpaw after immersion in 58 degrees C water for 1 min. Crude peptides, D-Leu-Ala-Thr-D-Tyr-Arg-Lys-Leu-Leu-Glu-Ile-D-Leu-NH2 and D-Ala-His-Ser-D-Asn-Arg-Lys-Leu-Leu-Glu-Ile-D-Leu-NH2, were found to have activity in this bioassay. Characterization of the structures within the crude mixture revealed that substitution of the glutamic acid residue with an anisolyated glutamic acid (2-amino-5-(methoxyphenyl)-5-oxopentanoic acid) derivative, designated as (A*), increased the overall potency. The glutamyl-anisole derivative was a by-product of the temperature-dependent Friedel-Crafts acylation reaction that occurs during hydrogen fluoride cleavage of glutamyl-containing peptides.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1993

Xenopsin, neurotensin, neurotensin(8-13) and N-acetyl-neurotensin(8-13) inhibit vascular leakage in rats after tissue injury.

Swelling, edema and leakage of proteins from the vascular compartment are immediate inflammatory responses of living tissues to local injury. Xenopsin, neurotensin (NT), NT(8-13) and NAcNT(8-13) administered to male rats anesthetized with sodium pentobarbital 60 mg/kg i.p. inhibited swelling and edema in the paw induced by immersion in 58 degrees water for 1 min. The ED50 values for xenopsin. NT, NAcNT(8-13) and NT(8-13) for reducing heat-induced edema were 0.9, 1.5, 1.9 and 2.1 nmol/kg i.v., respectively. NAcNT(8-13) was chosen as a prototype for further studies because, compared to NT, it had minimal hypotensive effects. NAcNT(8-13), 4 nmol/kg i.v., injected 10 min before mechanical injury to muscle, produced by a 4 cm midline surgical incision in the rectus abdominis, or before freeze injury to the cortex, produced by applying a cold probe (-50 degrees C) to the skull for 4 min, reduced vascular leakage, measured as area of Monastral blue staining of the injured tissues. NAcNT(8-13), 4 nmol/kg i.v., also attenuated pulmonary edema induced by epinephrine bitartrate 10 micrograms/kg i.v. The ability of NAcNT(8-13) to inhibit vascular leakage was not linked to its transient hypotensive effects and it was not blocked by alpha-helical-CRF(9-41), a putative CRF receptor antagonist, or by chlorpheniramine, a H1-histamine receptor antagonist.

Animals↗
PubMed1991

Corticotropin-releasing factor: an inhibitor of vascular leakage in rat skeletal muscle and brain cortex after injury.

Corticotropin-releasing factor (CRF) and other peptides of the corticoliberin superfamily inhibit development of edema in skin and mucosa after noxious stimuli. Here, the breadth of CRFs protective activity on small blood vessels was examined after injury to skeletal muscle or to brain cortex. Male rats (243 +/- 15 g) were anesthetized with sodium pentobarbital 60 mg/kg i.p. and Monastral blue 60 mg/kg i.v. was injected 3 min before mechanical injury to muscle produced by a 4 cm midline surgical incision in the rectus abdominis or before freeze injury to the cortex produced by applying a cold probe (-50 degrees C) to the skull for 4 min. Vascular leakage, measured as area of dye staining multiplied by its light intensity, was quantified with an image-analysis system. CRF, having the human/rat sequence, 30 micrograms/kg s.c., injected once (30 min) or twice (30 min and 10 min) before injury to muscle or to brain, inhibited the lesion size by 58% and 55%, respectively (tissues taken at 0.5 and 1 h). Microscopy showed that CRF inhibited Monastral blue labeling of small blood vessels. The ED50 (95% C.L.) of CRF for reducing vascular leakage in muscle after celiotomy was 24 (9 to 64) micrograms/kg s.c. h/rCRF injected 30 micrograms/kg s.c. 2 h before celiotomy inhibited vascular leakage after celiotomy in adrenalectomized rats and this effect was not obtained with dexamethasone phosphate, 1 mg/kg s.c. alpha-Helical CRF (9-41), a CRF receptor antagonist, attenuated the actions of CRF on celiotomy. Laser-Doppler flowmeter measurements of skeletal muscle showed that the anti-inflammatory effects of CRF occurred when there were no significant concurrent changes in blood flow. From these results, we surmise that CRF has a versatile protective effect on small blood vessels when it inhibits leakage within different vascular beds.

Animals↗
PubMed1991

Corticotropin-releasing factor inhibits the acute inflammatory response of rat pawskin to cold injury.

The anti-inflammatory effects of human/rat corticotropin-releasing factor (CRF), a 41-residue peptide hormone, on an experimental model of cold injury were examined. Male albino rats were anesthetized with sodium pentobarbital 60 mg/kg ip and the paws immersed for 1 or 2 min in a 22% NaCl solution maintained at -20 +/- 0.5 degrees C. Swelling in response to cold was measured by changes in paw volume using the fluid displacement method, and protein leakages from blood vessels were measured using Evans blue and Monastral blue dyes. Thirty minutes after cold exposure the paw volume increased from 1.5 +/- 0.1 to 2.4 +/- 0.1 ml/paw and the Evans blue content increased from 4 +/- 1 to 178 +/- 9 micrograms/pawskin. These responses to cold were inhibited by 40 to 60% after CRF was injected 56 micrograms/kg sc 30 min before or 28 micrograms/kg iv 10 min before or 5 min after cold exposures. Microscopic studies of the skin showed that CRF reduced leakage of Monastral blue pigment from the vascular compartment into the walls of capillaries and venules. The anti-inflammatory effects of CRF were blocked by alpha-helical CRF(9-41), a CRF receptor antagonist, injected 92 micrograms/kg iv 5 min before and 15 min before cold exposure.

Animals↗
PubMed1990

Decreased inflammatory responsiveness of hypophysectomized rats to heat is reversed by a corticotropin-releasing factor (CRF) antagonist.

Hypophysectomy, but not adrenalectomy, decreased (relative to sham-operated controls) the swelling and Evans blue dye extravasation responses of the anesthetized rat's pawskin to thermal injury. alpha-Helical CRF (9-41), a synthetic competitive antagonist of corticotropin-releasing factor (CRF) on isolated pituitary cells, did not affect in sham-operated rats the swelling response after immersion of the paw in 58 degrees C water for 30 s. Swelling was measured over a 1 h period using the fluid displacement method for quantifying paw volume. But, when alpha-helical CRF (9-41) was injected 92 micrograms/kg i.v. 10 min before or immediately after heat exposure, it both attenuated and reversed the insensitive state produced by hypophysectomy: that is, the swelling response reappeared. Under the same test conditions, naloxone hydrochloride, an opioid antagonist, was ineffective. The results suggest that hypophysectomy may induce a condition whereby endogenous CRF or CRF-like peptides may act as an anti-inflammatory agent.

Adrenalectomy↗
PubMed1989

Corticotropin-releasing factor inhibits the response of trigeminal neurons to noxious heat.

In a previous study we reported that human/rat corticotropin-releasing factor (CRF) displayed antinociceptive activity in the mouse abdominal constriction assay. In this investigation we examined the effects of CRF on the evoked response of wide dynamic range (WDR) trigeminal neurons to noxious heat. Single units were recorded from the spinal trigeminal nucleus of urethane anesthetized rats. CRF inhibited the evoked response of these units in a dose-dependent manner with an ED50 of 2.3-7 nmol/kg i.v. Neither naloxone nor chlorisondamine pretreatment prevented the inhibitory actions of CRF. CRF-induced inhibition was also present in adrenalectomized and hypophysectomized animals. Intracerebroventricular administration of CRF did not inhibit the heat evoked response of WDR trigeminal units. alpha-Helical CRF, a CRF receptor antagonist, 12 nmol/kg i.v., alone did not affect the response of trigeminal units to heat, but pretreatment of animals with this dose blocked the inhibitory actions of CRF. By contrast to the inhibitory effects of CRF on heat-responsive units, CRF, 6-18 nmol/kg i.v., increased the spontaneous discharge rate of cold-responsive units by 57 +/- 16%. The data show that CRF selectively inhibits neuronal responses to noxious heat, an action that is independent of the pituitary-adrenal axis. These results are viewed as further evidence that CRF has antinociceptive properties in the periphery.

Action Potentials↗
PubMed1989

Peptides of the corticoliberin superfamily attenuate thermal and neurogenic inflammation in rat pawskin.

The paws of pentobarbital-anesthetized rats were immersed in 48 or 58 degree C water for 5 min and the thermal inflammatory response to heat was measured by Evans blue dye leakage into the pawskin. Sauvagine, sucker fish urotensin I and human/rat corticotropin-releasing factor (CRF), homologous peptides belonging to the corticoliberin superfamily, injected i.v. 10 min before heat exposure, inhibited dye leakage with ED50 (nmol/kg) of 0.44, 1.5 and 5.9, respectively. The same rank order of potency was observed when the peptides were tested against the protein extravasation evoked by antidromic stimulation of the rat saphenous nerve. The alpha-helical CRF-(-9-41) antagonist, administered alone at 24 nmol/kg i.v., did not affect the heat-induced dye leakage into skin; but it attenuated the effects of h/rCRF, urotensin I and sauvagine. h/r[Tyr0]CRF, ovine[Nle21,Tyr32]CRF and h/r[Met(O)21,38]CRF, administered 24 nmol/kg i.v., did not affect the dye leakage response to heat. Peptides of the corticoliberin superfamily may have the unusual property of making small blood vessels less permeable when responding to injurious stimuli.

Amphibian Proteins↗
PubMed1989

Acute inflammatory response of the rat pawskin to acid injury is attenuated by corticotropin-releasing factor.

Increased vascular permeability, as measured by changes in skin weight and Evans blue dye extravasation, was produced in the skin after immersion of the anesthetized rat's paw in 12 N hydrochloric, 18N sulfuric, or 14N hydrofluoric acids for 2 min. Corticotropin-releasing factor (CRF), a 41-residue peptide having the rat/human sequence, injected 28 micrograms/kg i.v. 10 min before immersion, was efficacious in reducing these indices of skin injury.

Acids↗
PubMed1988

Protective actions of corticotropin-releasing factor on thermal injury to rat pawskin.

Corticotropin-releasing factor (CRF), a 41-residue peptide, inhibits the edema and protein extravasation produced by heat applied to the rat pawskin. Here, the time course of CRFs actions against heat-induced swelling was investigated. The paws of pentobarbital-anesthetized rats were immersed in 58 degrees C water for 30 sec and the resultant swelling was measured by the fluid displacement method. Human/rat CRF, 28 micrograms/kg s.c., injected 0.5 to 2 hr before heat exposure reduced swelling by over 50%. Pretreatment at 4 hr before heat was also effective, but not at 12 or 24 hr. CRF, injected 28 micrograms/kg i.v. 0, 10 or 20 min after heat exposure, inhibited the progressive development of swelling immediately. Histological examination of skin showed that CRF, given before or after heat, reduced vesication, edema, epidermal necrosis and the disruption of tissue architecture produced by thermal injury. The alpha-helical CRF(9-41) antagonist administered alone, 92 micrograms/kg i.v., before or after heat did not affect heat injury. The antagonist, however, both prevented and reversed the inhibitory effects of CRF on the swelling produced by heat. The antagonist-induced reversal occurred as late as 2 hr after CRF, 28 micrograms/kg s.c. Overall, these results suggested that CRF is a potent and efficacious agent in protecting skin against experimental thermal injury.

Animals↗
PubMed1987

Inhibition of protein exudation from the trachea by corticotropin-releasing factor.

Increased vascular permeability in the trachea, as measured by Evans blue dye leakage, was produced in the anesthetized rat by antidromic stimulation of the right vagus or by exposure to dilute formalin vapors. Corticotropin-releasing factor (CRF) inhibited tracheal protein extravasation at dosages of 6-24 nmol (29-114 micrograms)/kg i.v. injected 10 min before nerve stimulation or formaldehyde exposure. The decrease in respiration rate and blood pressure produced by formaldehyde was also attenuated by CRF.

Animals↗
PubMed1987

Corticotropin-releasing factor inhibits thermal injury.

Thermal injury to the skin increases transfer of plasma fluids and proteins into the interstitium. Here, protein extravasation and edema were produced by immersion of the anesthetized rat's paw in 48 degrees C or 58 degrees C water for 5 min. Protein extravasation was measured by Evans blue dye leakage into the skin and edema by increases in skin weights. Corticotropin-releasing factor (CRF), having the human/rat 41-amino acid sequence, was efficacious in reducing these indices of thermal injury. Injected i.v. at microgram doses or intradermally at nanogram doses, it inhibited the protein extravasation and edema produced by heat. The intradermal median inhibitory dose (ED50) of CRF against protein extravasation elicited by 48 degrees C water was 21.8 times lower than the i.v. ED50, indicating that CRF's actions occurred locally in the paw skin. Ovine-CRF and dynorphin A(1-13) injected i.v. inhibited the protein extravasation and edema induced by 58 degrees C water, but morphine, ethylketocyclazocine and FK 33,824 (a stabilized enkephalin analog) were not active at this temperature. CRF may be a powerful inhibitor of the acute inflammatory response of the skin to thermal irritation.

Animals↗
PubMed1986

Inhibition of the shake response in rats by adenosine and 2-chloroadenosine.

Shaking movements, similar to those made by a dog when wet, were elicited in rats by immersion in ice-water, injections of icilin, a chemical that produces sensations of cold, and naloxone-precipitated morphine withdrawal. Adenosine and 2-chloroadenosine produced dose-dependent inhibition of shaking to ice-water and icilin. The 2-chloroadenosine effect was mediated centrally because the ICV dose required to produce inhibition was not effective when given IP. Caffeine antagonized the inhibitory effects of adenosine and 2-chloroadenosine. 2-Chloroadenosine suppressed morphine-abstinence shaking as well as the body weight loss that normally accompanies withdrawal.

2-Chloroadenosine↗
PubMed1986

Corticotropin-releasing factor inhibits neurogenic plasma extravasation in the rat paw.

Increased exudation of plasma proteins, as measured by Evans blue leakage into the innervated paw, was produced by antidromic stimulation of the saphenous nerve in the pentobarbital-anesthetized rat. This condition, termed neurogenic plasma extravasation (NPE), was inhibited by morphine, FK 33,824 (a stabilized enkephalin analog), dynorphin (1-13), dynorphin(1-10)amide and corticotropin-releasing factor (CRF) at median effective doses of 2700, 0.45, 1180, 4050 and 5.6 nmol/kg i.v., respectively. The inhibitory effect of CRF was present when injected up to 60 min before electrical stimulation of the nerve. By contrast, the effects of morphine and FK 33,824 were shorter in duration, lasting for only 20 to 30 min before nerve stimulation. Inhibition of NPE by morphine, FK 33,824 dynorphin (1-13) and dynorphin (1-10)amide was blocked by naloxone, 1 mg/kg i.v., but the CRF inhibition was not affected. CRF inhibited NPE in both hypophysectomized and adrenalectomized rats, indicating that its effects were not due to secondary release of endogenous opioid peptides. The inhibitory effect of CRF on NPE was also separable from its hypotensive properties and could be obtained at intradermal doses of CRF into the paw skin which were approximately 11 times lower than the i.v. doses. Intracerebroventricular injection of CRF did not affect the tail-flick latency of rats to warm water. CRF administered i.v. in mice did, however, inhibit writhing responses to phenylbenzoquinone (PBQ), suggesting possible peripheral antinociceptive properties.

Adrenalectomy↗