Neurokinin-induced changes in pial artery diameter in the anaesthetized guinea-pig.
1. The effects of selective neurokinin agents on pial artery diameter, measured with an on-line image analyser, have been studied in anaesthetized guinea-pigs in order to characterize the neurokinin receptors present on pial arteries. 2. Perivascular injection of either substance P (0.01-1 microM) or the selective NK1 receptor agonists, substance P methyl ester (SPOMe, 0.01-1 microM) and GR73632 (0.1 microM), increased pial artery diameter. 3. In contrast, the selective NK2 receptor agonist, GR64349 (1 microM), produced a small vasoconstriction while the NK3 receptor-selective agonist, senktide (1 microM) was inactive. 4. Co-administration of GR82334 (1 microM), a selective NK1 receptor antagonist, inhibited the vasodilatation produced by SPOMe (0.1 microM) but not that caused by calcitonin gene-related peptide (CGRP, 0.01 microM). 5. The results are consistent with an involvement of NK1 receptors in the neurokinin-induced increase in guinea-pig pial artery diameter.
Beattie
D T
DT
Department of Neuropharmacology, Glaxo Group Research Ltd, Ware Herts.
Stubbs
C M
CM
Connor
H E
HE
Feniuk
W
W
D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D006168:Guinea Pigs; D008297:Male; D015288:Neurokinin A / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010803:Physalaemin / Q000031:analogs & derivatives / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply*; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*
D010446:Peptide Fragments; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; C079014:GR 82334; C068032:GR 73632; C068031:neurokinin A (3-10), lysyl(3)-glycyl(8)-R-lactam-leucine(9)-; D010803:Physalaemin; D013373:Substance P; C033611:substance P, methyl ester-; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide