Study of an adenosine A1 receptor agonist on trigeminally evoked dural blood vessel dilation in the anaesthetized rat.
The purpose of this study was to use intravital microscopy to determine the effect of a selective adenosine A1 receptor agonist, GR79236 (1, 3 and 10 microg/kg i.v.), on neurogenic dural blood vessel dilation in anaesthetized rats. Vasodilation was evoked either by electrical stimulation of perivascular trigeminal nerves or by intravenous CGRP. GR79236 (1-10 microg/kg i.v.) caused a dose-dependent inhibition of neurogenic vasodilation, but had no significant effect on dural vasodilation caused by CGRP. GR79236 (1-3 microg/kg i.v.) had no effect on basal dural vessel diameter, but caused transient dose-dependant bradycardia and hypotension. Bradycardia was more prolonged following 10 microg/kg i.v. GR79236. Pre-treatment with the adenosine A1 receptor antagonist DPCPX (1 mg/kg i.v.) prevented the inhibitory effect of GR79236 (10 microg/kg i.v.) on neurogenic vasodilation as well as GR79236-induced bradycardia and hypotension. These data suggest that the inhibition of neurogenic vasodilation by GR79236 is mediated via the activation of prejunctional adenosine A1 receptors. Provided the systemic cardiovascular effects could be limited, such a mechanism may offer a novel approach to migraine therapy.
Honey
A C
AC
The Headache Research Group, Glaxo Smith Kline R & D, Stevenage, UK. andrew_c_honey@gsk.com
Bland-Ward
P A
PA
Connor
H E
HE
Feniuk
W
W
Humphrey
P P A
PP
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000633:toxicity; D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000139:chemically induced; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D004388:Dura Mater / Q000098:blood supply*; D004558:Electric Stimulation; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000139:chemically induced; D008297:Male; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014276:Trigeminal Nerve / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology
D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; C051360:1,3-dipropyl-8-cyclopentylxanthine; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine