Activity of tachykinin NK1 and bradykinin B2 receptor antagonists, and an opioid ligand at different stimulation parameters in neurogenic inflammation in the rat.
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.
Towler
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PK
Pharmacology Group and Vascular Biology Research Centre, King's College London, UK.
Brain
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SD
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
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