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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

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.[1]

References

  1. In-depth characterization of CGRP receptors in human intracranial arteries. Jansen-Olesen, I., Jørgensen, L., Engel, U., Edvinsson, L. Eur. J. Pharmacol. (2003) [Pubmed]
 
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