Lack of effect of the adenosine A1 receptor agonist, GR79236, on capsaicin-induced CGRP release in anaesthetized pigs.
Migraine is a common neurological disorder that is associated with an increase in plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a potent vasodilator released from the activated trigeminal sensory nerves, dilates intracranial blood vessels and transmits vascular nociception. Hence, inhibition of trigeminal CGRP release may prevent neurotransmission and, thereby, ameliorate migraine headache. Therefore, the present study in anaesthetized pigs investigates the effects of a selective adenosine A(1) receptor agonist, GR79236 (3, 10 and 30 microg/kg, i.v.) on capsaicin-induced carotid haemodynamic changes and on plasma CGRP release. Intracarotid (i.c.) infusion of capsaicin (10 microg/kg/min, i.c.) increased the total carotid blood flow and conductance as well as carotid pulsations, but decreased the difference between arterial and jugular venous oxygen saturations. These responses to capsaicin were dose-dependently attenuated by GR79236. However, the increases in the plasma CGRP concentrations by capsaicin remained essentially unmodified after GR79236 treatment. The above results suggest that GR79236 may have an antimigraine potential due to its postjunctional effects (carotid vasoconstriction) rather than to prejunctional inhibition of trigeminal CGRP release.
Arulmani
U
U
Department of Pharmacology, Cardiovascular Research Institute COEUR, Erasmus MC, University Medical Centre Rotterdam, the Netherlands.
Heiligers
J P C
JP
Centurión
D
D
Garrelds
I M
IM
Villalón
C M
CM
Saxena
P R
PR
D000241:Adenosine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D058907:Adenosine A1 Receptor Agonists; D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D015740:Calcitonin Gene-Related Peptide / Q000097:blood* / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002339:Carotid Arteries / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D007261:Infusions, Intra-Arterial; D010100:Oxygen / Q000097:blood; D034421:Sus scrofa
D058907:Adenosine A1 Receptor Agonists; D015740:Calcitonin Gene-Related Peptide; D000241:Adenosine; C082299:N-((1S,trans)-2-hydroxycyclopentyl)adenosine; D002211:Capsaicin; D010100:Oxygen