CHARACTERIZATION OF THE RECEPTOR MEDIATING RELAXATION TO SUBSTANCE-P IN CANINE MIDDLE CEREBRAL-ARTERY - NO EVIDENCE FOR INVOLVEMENT OF SUBSTANCE-P IN NEUROGENICALLY MEDIATED RELAXATION

Citation
Cm. Stubbs et al., CHARACTERIZATION OF THE RECEPTOR MEDIATING RELAXATION TO SUBSTANCE-P IN CANINE MIDDLE CEREBRAL-ARTERY - NO EVIDENCE FOR INVOLVEMENT OF SUBSTANCE-P IN NEUROGENICALLY MEDIATED RELAXATION, British Journal of Pharmacology, 105(4), 1992, pp. 875-880
Citations number
40
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
875 - 880
Database
ISI
SICI code
0007-1188(1992)105:4<875:COTRMR>2.0.ZU;2-C
Abstract
1 The aim of this study was to characterize the neurokinin receptor wh ich mediates relaxation of dog isolated middle cerebral artery by the use of selective agonists and antagonists and to establish whether sub stance P is involved in the neurogenically mediated relaxant response in this vessel. 2 Substance P caused concentration-related, endotheliu m-dependent relaxations of dog isolated middle cerebral artery, contra cted with prostaglandin F2-alpha. The selective NK1 receptor agonists, GR73632 and substance P methyl ester (SPOMe), also caused relaxation with similar maximum effects to those of substance P. GR73632 and SPOM e were approximately 20 times and 6 times less potent respectively tha n substance P. The selective NK2 and NK3 receptor agonists, GR64349 an d senktide, were only weakly active in causing relaxation being at lea st 425 times and 245 times less potent respectively than substance P. 3 The selective NK1 receptor antagonist, GR82334, was a potent, specif ic, competitive antagonist of the relaxant effects of substance P. In contrast, the selective NK2 receptor antagonist, R396 (10-mu-M) had no effect on the response to substance P. 4 Electrical field stimulation of dog isolated middle cerebral artery, contracted with prostaglandin F2-alpha, caused neurogenically mediated, non-adrenergic non-choliner gic (NANC) relaxations. These NANC relaxations were unaffected by endo thelium removal, GR82334 (10-mu-M) or by capsaicin (10-mu-M) treatment . However, the nitric oxide synthesis inhibitor, L-N(G)-monomethyl arg inine methyl ester (L-NMMA) (100-mu-M) markedly attenuated the respons e to electrical stimulation. 5 These results suggest that substance P causes relaxation of dog isolated middle cerebral artery via activatio n of NK1 receptors. However, substance P does not appear to be involve d in NANC neurotransmission. In contrast, the marked inhibitory effect of L-NMMA on NANC relaxations implicates nitric oxide in NANC neurotr ansmission in this vessel.