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Involvement of sensory neuropeptides in the development of plasma extravasation in rat dorsal skin following thermal injury
Author(s) -
Siney L.,
Brain S.D.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16698.x
Subject(s) - extravasation , calcitonin gene related peptide , chemistry , antagonist , endocrinology , medicine , receptor , neuropeptide , pathology
1 The involvement of the neuropeptides, substance P (SP) and calcitonin gene‐related peptide (CGRP) in plasma extravasation following thermal injury of rat dorsal skin was investigated. 2 Heat applied to the dorsal skin of anaesthetized rats by a temperature‐controlled skin heater (1 cm diameter) for 5 min induced temperature‐dependent plasma protein extravasation at 46°C to 50°C measured over the 20 min following initiation of heat. 3 The NK 1 ‐receptor antagonist, SR140333, at doses above 36 nmol kg −1 , significantly ( P < 0.05) inhibited plasma extravasation by up to 79 ± 3% (120 nmol kg −1 ) after heat application at 48°C and by up to 53 ± 10% (120 nmol kg −1 ) after heat application at 50°C. 4 The CGRP 1 ‐receptor antagonist, CGRP 8–37 , at doses of 200 and 400 nmol kg −1 , significantly inhibited ( P < 0.01) plasma extravasation by 55 ± 9 and 60 ± 12%, respectively, after heat application at 48°C. At a dose of 200 nmol kg −1 CGRP 8–37 inhibited plasma extravasation by 41 ± 8% after heat application at 50°C. 5 SR140333, 120 nmol kg −1 , and CGRP 8–37 , 200 nmol kg −1 together significantly ( P < 0.01) inhibited plasma extravasation by 84 ± 15% after heating at 48°C for 5 min. 6 In experiments where the response was measured for 0–5, 5–10, 10–15 or 15–20 min, SR140333, 120 nmol kg −1 , significantly ( P < 0.05) inhibited plasma extravasation which had accumulated during all the time periods measured. In comparison, CGRP 8–37 , 200 nmol kg −1 , was significantly ( P < 0.05) effective at time‐points up to 15 min after initiation of injury. 7 In longer term experiments plasma protein extravasation continued for at least 95 min after initiation of thermal injury. SR140333, at a dose of 120 nmol kg −1 , significantly inhibited plasma extravasation for up to 65 min after initiation of injury. 8 In conclusion, the data from the present study demonstrate that both SP and CGRP are likely to have a role in the acute plasma extravasation after thermal injury. In addition, evidence suggests SP may have a role in plasma extravasation for up to 65 min.