In-depth characterization of CGRP receptors in human intracranial arteries.
The purpose of the present study was to characterize the effects of human (h) alpha- and beta-calcitonin gene-related peptide (CGRP) on intracranial arteries from man and to investigate the presence of mRNA for the calcitonin receptor like receptor (CRLR) and the receptor activity modifying proteins (RAMPs) 1, 2 and 3, in cerebral and middle meningeal arteries with and without endothelium, in microvessels and in the endothelial cells isolated from the human basilar artery. Reverse transcriptase-polymerase chain reaction (RT-PCR) revealed the presence of CRLR, RAMP 1, RAMP 2 and RAMP 3 in cerebral and middle meningeal arteries with and without endothelium as well as in microvessels and in the endothelial cells. Human and rat alpha- and beta-CGRP, amylin, adrenomedullin and [acetamidomethyl-Cys(2,7)]human CGRP induced strong concentration-dependent relaxation of human cerebral and middle meningeal arteries. Removal of the endothelium neither changed the maximum relaxant response nor the pIC(50) values for alpha- and beta-CGRP as compared to the responses in arteries with an intact endothelium. Human alpha-CGRP-(8-37) caused a shift of h alpha- and h beta-CGRP-induced relaxations in cerebral and middle meningeal arteries. Calculation of pK(B) values revealed that h alpha-CGRP-(8-37) could not significantly discriminate between relaxations induced by h alpha-CGRP (pK(B) around 6.8) and h beta-CGRP (pK(B) around 5.4). There was no significant difference in pK(B) value of h alpha-CGRP-(8-37) on h beta-CGRP-induced relaxation of human cerebral and middle meningeal arteries with and without endothelium. In conclusion, our molecular and pharmacological data support the existence of a single type of CGRP(1) receptors in the human intracranial circulation.
Jansen-Olesen
Inger
I
Department of Neurology, Glostrup Hospital, Nordre Ringvej 57 Dk-2600 Glostrup, Denmark. ijo@tdacadsl.dk
Jørgensen
Linda
L
Engel
Ulla
U
Edvinsson
Lars
L
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002536:Cerebral Arteries / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000098:blood supply* / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008576:Meningeal Arteries / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D008833:Microcirculation / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000819:agonists / Q000032:analysis* / Q000096:biosynthesis; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide