Tachykinins (substance P, neurokinin A, neuropeptide K, and neurokinin B) in the cerebral circulation: vasomotor responses in vitro and in situ.
The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP greater than NKB greater than NKA greater than NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB greater than NKA = NPK; and in the guinea pig basilar artery, SP much greater than NPK = NKA greater than NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration-response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig.(ABSTRACT TRUNCATED AT 250 WORDS)
Jansen
I
I
Department of Experimental Research, Malmö General Hospital, Sweden.
Alafaci
C
C
McCulloch
J
J
Uddman
R
R
Edvinsson
L
L
D000818:Animals; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology; D006168:Guinea Pigs; D006801:Humans; D015288:Neurokinin A / Q000494:pharmacology*; D015287:Neurokinin B / Q000494:pharmacology*; D009479:Neuropeptides / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015320:Tachykinins; D014664:Vasodilation / Q000187:drug effects*
D009479:Neuropeptides; D015320:Tachykinins; C045206:neuropeptide K; D013373:Substance P; D015288:Neurokinin A; D015287:Neurokinin B; C042867:spantide