Activation of sensory nerves in guinea-pig isolated basilar artery by nicotine: evidence for inhibition of trigeminal sensory neurotransmission by sumatriptan.
Nicotine (100 microM), but not electrical field stimulation or potassium chloride (0.1-3 microM), caused capsaicin (1 microM)- and tetrodotoxin (1 microM)-sensitive relaxations of guinea-pig isolated basilar artery precontracted with prostaglandin F2 alpha. Nicotine-induced responses were blocked by the neurokinin NK1 receptor antagonist, GR82334 (10 microM), but were unaffected by the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP-(8-37) (1 microM). This suggests that nicotine activates capsaicin-sensitive sensory nerves in guinea-pig basilar artery to cause relaxation predominantly via substance P release. The vascular 5-HT1 receptor agonist, sumatriptan (0.3 and 3 microM), inhibited nicotine-induced relaxation (by 50 and 80% respectively); the inhibitory effect of sumatriptan (0.3 microM) was attenuated in the presence of the non-selective 5-HT1 receptor antagonist, methiothepin (0.1 microM). These data suggest that sumatriptan can inhibit sensory neurotransmission in guinea-pig basilar artery via activation of inhibitory prejunctional 5-HT1 receptors on sensory nerve terminals.
O'Shaughnessy
C T
CT
Pharmacology 2 Department, Glaxo Research & Development Ltd., Ware, Herts, UK.
Connor
H E
HE
D000818:Animals; D001488:Basilar Artery / Q000294:innervation*; D000068438:Brimonidine Tartrate; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018170:Sumatriptan / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D014276:Trigeminal Nerve / Q000502:physiology
D010446:Peptide Fragments; D011810:Quinoxalines; C058636:calcitonin gene-related peptide (8-37); D000068438:Brimonidine Tartrate; D011189:Potassium Chloride; D009538:Nicotine; D018170:Sumatriptan; D015740:Calcitonin Gene-Related Peptide