title: Activity of tachykinin NK1 and bradykinin B2 receptor antagonists, and an opioid ligand at different stimulation parameters in neurogenic inflammation in the rat.
abstract: Stimulation of the saphenous nerve in the anaesthetised rat results in cutaneous neurogenic oedema formation. We have examined the effect of a tachykinin NK1 and a bradykinin B2 antagonist, and a mu-opioid agonist on plasma extravasation observed in response to two differing nerve stimulating parameters (10 V, 1 ms, 2 Hz and 25 V, 2 ms, 10 Hz). The NK1 antagonist SR140333 abolished oedema, supporting the theory that an NK1 agonist is a primary mediator of neurogenic oedema. The B2 antagonist HOE 140 had no effect, indicating a lack of involvement of B2 receptors in this response. The pre-junctionally acting mu-opioid agonist DAMGO significantly inhibited oedema formation at the 10 V, 1 ms, 2 Hz (P < 0.001), but not the 25 V, 2 ms, 10 Hz stimulation parameters. Thus a post-junctionally acting NK1 antagonist inhibited neurogenic oedema formation induced by both stimulation parameters, whilst a pre-junctionally acting mu-opioid agonist acted only at 10 V, 1 ms, 2 Hz parameters. These findings could be of interest with respect to therapeutic approaches of pathophysiological conditions which involve a neurogenic component.
authors.affiliation: Pharmacology Group and Vascular Biology Research Centre, King's College London, UK.
authors.forename: P K
authors.initials: PK
authors.lastname: Towler
authors.forename: S D
authors.initials: SD
authors.lastname: Brain
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000031:analogs & derivatives / Q000627:therapeutic use; D065168:Bradykinin Receptor Antagonists; D004487:Edema / Q000378:metabolism; D004558:Electric Stimulation; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000627:therapeutic use; D005119:Extravasation of Diagnostic and Therapeutic Materials / Q000188:drug therapy; D008297:Male; D020078:Neurogenic Inflammation / Q000188:drug therapy*; D064729:Neurokinin-1 Receptor Antagonists; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000627:therapeutic use; D011812:Quinuclidines / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D043782:Receptor, Bradykinin B2; D018040:Receptors, Neurokinin-1 / Q000819:agonists; D017450:Receptors, Opioid, mu / Q000819:agonists; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D065168:Bradykinin Receptor Antagonists; D004745:Enkephalins; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D043782:Receptor, Bradykinin B2; D018040:Receptors, Neurokinin-1; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C068032:GR 73632; C085215:SR 140333; D013373:Substance P; C065679:icatibant; D001920:Bradykinin