Presence and function of the calcitonin gene-related peptide receptor on rat pial arteries investigated in vitro and in vivo.
Calcitonin gene-related peptide (CGRP) and related peptides may be involved in migraine pathogenesis. To understand their vasomotor role in the cerebral circulation, we performed two studies, a pressurized arteriography study of the middle cerebral artery (MCA) and a genuine closed cranial window (gCCW) in vivo study. Using the pressurized arteriography model rat MCAs were mounted on micropipettes, pressurized to 85 mmHg and luminally perfused. The diameter responses to luminally and abluminally applied rat-alphaCGRP, rat-betaCGRP, amylin and adrenomedullin were compared with the resting diameter. Only abluminally applied CGRP induced dilation of the cerebral arteries; E(max) for alphaCGRP and betaCGRP were 35 +/- 0.5% and 10.8 +/- 0.2%. These responses were blocked by CGRP(8-37). The gCCW model allowed videomicroscopic visualization of the pial vessels in anaesthetized rats. Changes in vessel diameter to intravenously administered alphaCGRP and betaCGRP were compared with pre-infusion baseline. Intravenous infusion of alphaCGRP and betaCGRP in the highest dose induced dilation of the cerebral cortical pial arteries/arterioles of 40.3 +/- 7.5% and 49.1 +/- 8.4%, respectively. However, this was probably secondary to a decrease in blood pressure of 44.8 +/- 3.3 mmHg and 49.2 +/- 3.3 mmHg. Our results suggest that CGRP receptors are probably functional on the smooth muscle cells and not on the endothelium of rat cerebral arteries.
Petersen
K A
KA
Danish Headache Center, University of Copenhagen, Denmark. kapetersen@dadlnet.dk
Nilsson
E
E
Olesen
J
J
Edvinsson
L
L
D053607:Adrenomedullin; D000682:Amyloid / Q000378:metabolism / Q000494:pharmacology; D000792:Angiography; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D058228:Islet Amyloid Polypeptide; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D010841:Pia Mater / Q000098:blood supply* / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism*; D014664:Vasodilation; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D010455:Peptides; D018015:Receptors, Calcitonin Gene-Related Peptide; D014665:Vasodilator Agents; D053607:Adrenomedullin