The inhibition of substance P, neurokinin a and allergic oedema formation in guinea-pig skin by RP67580

196 in female rats). Intravenous injection of bradykinin (1 mol.&g) or substance P (3 nmol/kg) produced plasma protein extravasation, measured by the Evans blue leakage technique, in the rat urinary bladder. The response to bradykinin was prevented by Hoe 140 (100 nmovkg i.v.) andunaffectedby (&) CP 96,345 (10 prnol/kg i.v.). Plasma protein extravasation produced by substance P was inhibited by (&) CP 96,345 but was unchanged by Hoe 140. Catheterization required for xylene instillation into the female rat bladder produced per se an inflammatory response which was abolished by either Hoe 140 or (*) CP 96,345. Intravesical instillation of xylene (30%) in silicone oil, 15 min before) produced a large plasma protein extravasation which was reduced by about 65% by Hoe 140 or (&) CP 96,345. The combined administration of the two antagonists produced an additive effect on the plasma extravasation response to intravesical xylene. We conclude that both bradykinin and tachykinins are involved in the inllammatory reaction of the rat urinary bladder to catheterization and xylene irritation.

Cl? Substance P and Somatostatin mRNA Expression During an Acute and Chronic Monoarthritis of the Hat Ankle Joint; a Nonradioactive in situ-hybridization Study B. Heppelrnann, F. Blecher, U. Hanesch, H.-G. Schaible, P. C. Emson* Physiologisches Institnt der Universitiit Wtirzburg, Rijntgenring 9, D-8700 Wtirzburg, FRG and *MRC Group, AFRC Institute of Animal Physiology and Genetics Research, Babraham, Cambridge CB2 4AT, UK Some neuropeptides in primary afferents play a role in the processing of sensory information in the central nervous system and in neurogenic mechanisms of inllammation. In the present study we examined whether the proportion of substance P (SP)- and somatostatin (SOM)-mRNA expressing dorsal root ganglion cells is altered in the course of a Freund’s adjuvant induced monoarthritis using a non-radioactive in situ-hybridization technique. Rats with inflamed ankle joints were perfused 2 and 20 days post inoculation. 5 pm paraffm sections of dorsal root ganglia L4-L6 were hybridized for SP- and SOM-mRNA. In dorsal root ganglion cells of the unaffected contralateral side, a positive in situ hybridization signal was found in 12.7% (SP-mRNA) and 7.7% (SOM-mRNA) of the perikarya. On the ipsilateral inflamed side the proportion of SP-mRNA containing afferents significantly increased to 16.6% (day 2) and 14.8% (day 20). The proportion of SOM-mRNA expressing afferents remained constant with 7.2% (day 2) and 8.0% (day 20). The present data demonstrate that inflammatory stimuli have different intluences on the neuropeptide synthesis in primary afferents. We, therefore, suggest that SP and SOM may play different roles in the development and maintenance of arthritis.

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C9 The Inhibition of Substance P, Neurokinin A and Allergic Oedema Formation in Guineapig skin by HP67580 S. D. Brain and P. Wilsoncroft Pharmacology Group, Division of Biomedical Sciences, King’s College, Manresa Road, London SW3 6LX, UK We have investigated the ability of the neurokinin-1 receptor antagonist RP67580 to inhibit oedema formation induced by infIammatory mediators and in an allergic inilammatory response. Oedema formation was measured in response to intradermally-injected (i.d.) agents by the extravascular accumulation of intravenously-injected lz51albumin in anaesthetised (sodium pentobarbitone, 30-50 mgkg i.p.) male Dunkin Hartley guinea-pigs. An acute allergic response (passive cutaneous anaphylaxis, PCA) was investigated as follows:- guinea-pigs were sensitized by i.d. guinea-pig anti-ovalbumin( lCcg/site and challenged 24 h later with ovalbumin (l@ite). RI’67580 i.d. inhibited oedema at sites which also received subtance P (3-30pmol; p < 0.05) neurokinin A (10Opmol; p < 0.01); but had no inhibitory effect on oedema induced by bradykinin (lO-1OOpmol) or histamine (10 nmol). These results suggest that RP67580 is a selective antagonist at the neurokinin-1 receptor when injected i.d. and that bradykinin does not induce oedema formation via neurokinin release in guinea-pig skin. However, RP67580 (10 nmol/site) significantly inhibited oedema formation in the PCA (56.8 f 7.2$/site inhibited to 39.7 f 6.8pl/site, mean f S.E.M. n = 7 p < 0.05). Thus neurokinins may, at least in part, mediate oedema formation in allergic responses in skin. We thank Rhone Poulenc Rorer for RP67580.

Cl0 The Peptidergic Innervation of the Human Superficial Temporal Artery: Immunohistochemistry, Ultrastructure and Vasomotility I. Jansen, S. Gulbenkian, A. Valenca, J. L. Antunes, J. Wharton, J. M. Polalc, L. Edvinsson Department of Experimental Research, General Hospital, S-214 01 Malmij, Sweden The peptidergic innervation of the human superficial temporal artery was investigated by means of immunohistochemical, ultrastructural and in vitro pharmacological techniques. The majority of nerve fibres displayed immunoreactivity (IR) for tyrosine hydroxylase, a marker for cathecholamines, and neuropeptide Y (NPY). A moderate supply displayed either acetylcholinesterase activity or IR for vasoactive intestinal peptide (VIP), peptide histidine methionine-27 (PHM) andcalcitoningene-relatedpeptide (CGRP). Only a few nerve fibres displayed substance P (SP), neurokinin A (NKA) and neuropeptide K (NPK)IR. In double stained preparations SP-IR was co-localized