BIBN4096BS is a potent competitive antagonist of the relaxant effects of alpha-CGRP on human temporal artery: comparison with CGRP(8-37).
Release of CGRP during migraine may produce harmful dilatation of cranial arteries, thereby possibly causing pain. We have compared the antagonism by BIBN4096BS and CGRP(8-37) of the relaxant effects of alpha-CGRP on rings of human temporal artery. alpha-CGRP relaxed the arteries precontracted with 9 - 24 mM KCl (-logEC50=9.4) nearly as efficaciously as sodium nitroprusside (10 microM). BIBN4096BS (0.1 - 100 nM) antagonized the effects of alpha-CGRP in surmountable manner with slopes of Schild-plots not different from unity. -LogKB values of 10.1 and 10.4 were estimated for BIBN4096BS when administered before or during the KCl-contracture respectively. BIBN4096BS (1 microM) did not modify the relaxant effects of papaverine and sodium nitroprusside. CGRP(8-37) (1 - 10 microM) antagonized the effects of alpha-CGRP in a surmountable manner with slopes of Schild-plots not different from unity. -LogKB values of 6.6 and 6.7 were estimated for CGRP(8-37) administered before or during the KCl-contracture respectively. The high affinity of BIBN4096BS for CGRP receptors of human temporal artery makes it an excellent tool to explore the hypothesis of CGRP-evoked cerebral vasodilation in migraine.
Verheggen
Raphaela
R
Department of Neurosurgery, University of Göttingen, 37075 Göttingen, Germany.
Bumann
Katja
K
Kaumann
Alberto J
AJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009599:Nitroprusside / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000187:drug effects; D013699:Temporal Arteries / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D010446:Peptide Fragments; D010879:Piperazines; D011799:Quinazolines; D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; C058636:calcitonin gene-related peptide (8-37); D009599:Nitroprusside; D010208:Papaverine; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant