A second form of human calcitonin gene-related peptide which is a potent vasodilator.

A recently predicted form of human calcitonin gene-related peptide, (beta CGRP) exhibits potent vasodilator activity in rabbit skin with a similar potency to the form of human CGRP originally described (alpha CGRP). Both peptides, because of their vasodilator activity, cause a potentiation of inflammatory oedema induced by mediators of increased vascular permeability. The results demonstrate that changes can be made at certain positions in the amino acid sequence of human CGRP without loss of vasodilator activity.

Inflammatory oedema induced by synergism between calcitonin gene-related peptide (CGRP) and mediators of increased vascular permeability.

The potent vasodilator calcitonin gene-related peptide (CGRP, human synthetic), when mixed with histamine and injected intradermally in the rabbit, induced a marked potentiation of local oedema. CGRP also potentiated oedema induced by other mediators of increased microvascular permeability in the rabbit; bradykinin, platelet-activating factor (Paf), C5a des Arg, N-formylmethionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4). Substance P alone, or mixtures of substance P and CGRP, failed to induce oedema in rabbit skin.

Lipoxygenase products of arachidonic acid in human inflamed skin.

Monohydroxy acids (HETEs) and leukotriene B4 (LTB4) metabolites of arachidonic acid were measured in skin of healthy volunteers after ultraviolet B irradiation, and in the uninvolved skin of psoriatics after topical dithranol application. Exudate was collected from suction bullae on control and inflamed abdominal skin, and analysed for 12-HETE and PGE2 by GC-MS and LTB4 by bioassay. 12-HETE and PGE2 were raised at 24 h but not at 72 h after u.

Ethological analyses of the effects of naloxone and the opiate antagonist ICI 154, 129 on social interactions in male house mice.

The influences of the mu blocker naloxone and the novel opioid delta receptor antagonist ICI, 154, 129 on videotaped encounters between individually-housed, male Swiss mice and anosmic male 'standard opponents' were assessed using a variety of ethological analyses. The effects of drugs were studied on individual elements and on the times allocated by subjects to broad categories of behaviour. Neither of the drugs significantly altered times allocated to broad categories of behaviour.

The role of leaf resin in the interaction between Eriodictyon californicum (Hydrophyllaceae) and its herbivore, Trirhabda diducta (Chrysomelidae).

The chaparral shrub Eriodictyon californicum secretes a phenolic leaf resin composed of flavonoid aglycones. We used leaves with artificially altered resin contents to test the effects of resin on the feeding, growth, and oviposition of the specialist herbivore Trirhabda diducta. In addition, we compared Trirhabda feeding and growth on young foliage with that on foliage from the preceding year.

Leukotrienes C4 and D4 in psoriatic skin lesions.

Chemoattractant arachidonate lipoxygenase products have been recovered from the skin lesions of psoriasis, and may play a role in eliciting the intra-epidermal neutrophil infiltrate that characterises this disease. In view of evidence for lipoxygenase activity in psoriasis, the characteristic vasodilation in psoriatic lesions, and the vasodilator properties of leukotriene (LT) C4 and D4 in human skin, the presence of these LTs in psoriatic lesions has been investigated. Skin chamber fluid from abraded psoriatic lesions contained significantly greater amounts of immunoreactive material than that from clinically normal skin, as determined by a double antibody radioimmunoassay (RIA) that uses antiserum cross-reacting with both LTC4 and LTD4.

Calcitonin gene-related peptide is a potent vasodilator.

A novel peptide, calcitonin gene-related peptide (CGRP), has been predicted to result from alternative processing of the primary RNA transcript of the calcitonin gene in the rat. Several lines of evidence suggest that CGRP is a transmitter in the central and peripheral nervous system. Human CGRP has been isolated and characterized, and shown to have potent effects on the heart.

The effect of etretinate on the cyclo-oxygenase and lipoxygenase products of arachidonic acid metabolism in psoriatic skin.

Eight psoriatic patients were treated with etretinate (50 mg daily) for 6 weeks. Skin chamber exudates from involved and uninvolved skin were assayed for arachidonic acid, 12-HETE, PGE2 and for neutrophil chemokinetic activity co-chromatographing with leukotriene B4, before and at weekly intervals during therapy. Pre-treatment concentrations of arachidonic acid, 12-HETE and leukotriene B4-like chemokinetic activity but not of PGE2 were elevated in involved skin when compared to uninvolved skin.

Leukotriene B4-like material in scale of psoriatic skin lesions.

Acidic lipid extracts of scale from the lesions of the skin disease, psoriasis, were purified by straight phase high performance liquid chromatography (h.p.l.

Levels of arachidonic acid and its metabolites in the skin in human allergic and irritant contact dermatitis.

Increased concentrations of arachidonic acid and prostaglandin E2, but not 12-hydroxy-eicosatetraenoic acid, were found in the skin in human contact dermatitis due to nickel and chromate allergens. Significant levels of neutrophil chemokinetic activity, with similar properties to leukotriene B4, were found in a high proportion of exudates from inflamed skin treated with allergen but not in exudates from untreated skin. Neither arachidonic acid nor its metabolites were increased in primary irritant dermatitis due to benzylalkonium chloride.

The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis.

The 5,12-dihydroxy metabolite of arachidonic acid, leukotriene B4, is a highly potent neutrophil chemoattractant. In view of the characteristic epidermal neutrophil infiltrate in psoriasis, the presence of leukotriene B4 in samples from untreated lesional and uninvolved skin has been sought. Chambers were fixed to abraded skin and filled with phosphate-buffered saline (PBS).

Production of intraepidermal microabscesses by topical application of leukotriene B4.

Leukotriene B4 is a highly potent leukocyte chemotactic compound. It has been identified in chamber fluid and scale from psoriatic skin lesions, in which epidermal neutrophil infiltration is reported to be one of the earliest pathologic events. The ability of leukotriene B4 to reproduce the inflammatory events of psoriasis, by topical application to the skin of normal human volunteers, was thus studied.

Comparison of the influence of the opiate delta receptor antagonist, ICI 154,129, and naloxone on social interaction and behaviour in an open field.

The influence of a novel opiate delta receptor antagonist, ICI 154,129, and naloxone on social interaction and on behaviour in an open field were compared. At a dose thought to optimally block the delta receptor, ICI 154,129 produced open field behaviour typical of a non-emotional animal: this drug decreased social investigation and the latency to attack. In contrast, naloxone was largely without effect in these tests.

Comparison in the mouse of the effect of the opiate delta receptor antagonist ICI 154129 and naloxone in tests of extinction, passive avoidance and food intake.

The effects of 30 and 80 mg/kg ICI 154,129, an opiate delta receptor antagonist, were compared with those of 0.1 and 10 mg/kg naloxone using tests of food-intake, passive avoidance and extinction in mice. Whereas naloxone depressed food intake and facilitated extinction, ICI 154,129 failed to affect food intake, passive avoidance or extinction although the mice reared significantly more during the test of food intake.

The identification of hydroxy fatty acids in psoriatic skin.

Psoriasis is a common chronic inflammatory and proliferative skin disease characterised by epidermal neutrophil infiltration which may be induced by chemotactic substances in the involved epidermis. Superficial psoriatic scale was shown to contain biologically active amounts of leukotriene B4 and monohydroxy-eicosatetraenoic acid (HETE)-like material as determined by assay for chemokinetic activity in high performance liquid chromatography (HPLC) fractions of scale extracts. Extracts of scale and chamber fluid from abraded lesional and uninvolved psoriatic skin were purified by HPLC and appropriate fractions were analysed by gas chromatography - mass spectrometry (GC-MS).