The involvement of calcitonin gene-related peptide (CGRP) and substance P in feline pial artery diameter responses evoked by capsaicin.
The effects of capsaicin and selective neuropeptide antagonists on pial artery diameter were measured using an on-line image analyser in anaesthetised cats, in order to monitor the effects of mediators released in response to activation of trigeminal nerves. Perivascular injection of CGRP (10(-8) M) and the neurokinin-1 (NK1) receptor agonist substance P methyl ester, SPOMe (10(-6) M) produced an increase in pial artery diameter. The vasodilatory action of these agonists was significantly and selectively inhibited using the CGRP receptor antagonist, CGRP8-37 (10(-6) M), and the NK1 receptor antagonist, CP99994 (10(-6) M) respectively. Capsaicin (10(-8)-10(-5) M) produced a biphasic response upon perivascular injection that was concentration dependent. At 10(-6) M capsaicin an initial transient vasoconstriction was observed followed by a longer-lasting vasodilatation. The vasodilator component was significantly reduced by CGRP8-37 (10(-6) M) or CP99994 (10(-6) M). These results show that chemical (capsaicin) activation of trigeminal nerves leads to vasodilatation of feline arteries in situ. This vasodilatation is mediated via the activation of CGRP and NK1 receptors probably via the efferent release of CGRP and a substance P-like peptide.
Pharmacology Group, King's College, London, UK.
K J
KJ
Escott
H E
HE
Connor
S D
SD
Brain
D T
DT
Beattie
D000777:Anesthetics; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology*; D002415:Cats; D002536:Cerebral Arteries / Q000187:drug effects*; D005260:Female; D007275:Injections, Intravenous; D008297:Male; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology*; D014276:Trigeminal Nerve / Q000187:drug effects; D014666:Vasomotor System / Q000187:drug effects*
D000777:Anesthetics; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; C080755:3-(2-methoxybenzylamino)-2-phenylpiperidine; D013373:Substance P; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin