Investigation of the role of tachykinin NK1, NK2 receptors and CGRP receptors in neurogenic plasma protein extravasation in dura mater.
The aim of this study was to investigate the role of tachykinin NK1 and NK2 receptors, and calcitonin gene-related peptide (CGRP) receptors in neurogenic plasma protein extravasation, induced by electrical stimulation of the trigeminal ganglion, in dura mater of anaesthetised rats and guinea-pigs. This response was significantly (P < 0.05) blocked in both species by the selective peptide tachykinin NK1 receptor antagonist, GR82334 ([D-Pro9[spiro-gamma-lactam]Leu10,Trp11]physalaemin-(1-11)) (0.02-0.2 mg/kg i.v.) whilst the selective tachykinin NK2 receptor antagonist, (+/-)-SR 48968 ((S)-N-methyl-N-[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4- dichlorophenyl) butyl] benzamide) (1 mg/kg i.v.) was without effect. The CGRP receptor antagonist, alpha-CGRP-(8-37) (0.1 mg/kg i.v.) significantly (P < 0.05) blocked this response in dura mater of guinea-pigs but not rats. These results suggest that substance P, acting via tachykinin NK1 rather than NK2 receptors, mediates neurogenic plasma protein extravasation in dura mater and that CGRP may have an involvement in this response in guinea-pigs.
O'Shaughnessy
C T
CT
Pharmacology 2 Department, Glaxo Research & Development Ltd., Ware, Herts, UK.
Connor
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HE
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001798:Blood Proteins / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004388:Dura Mater / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D005119:Extravasation of Diagnostic and Therapeutic Materials; D006168:Guinea Pigs; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments / Q000494:pharmacology; D010803:Physalaemin / Q000031:analogs & derivatives* / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects / Q000502:physiology*; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*
D001549:Benzamides; D001798:Blood Proteins; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D018015:Receptors, Calcitonin Gene-Related Peptide; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; C058636:calcitonin gene-related peptide (8-37); C079014:GR 82334; D010803:Physalaemin; C073839:SR 48968; D015740:Calcitonin Gene-Related Peptide