Evidence for CGRP re-uptake in rat dura mater encephali.
OBJECTIVE
Calcitonin gene-related peptide (CGRP) is widely distributed in the trigeminovascular system and released from sensory fibres of the cranial dura mater upon noxious stimulation. Such release may be a mechanism underlying migraine headache. Based on data from guinea pig basilar artery preparations, we have here studied CGRP release and uptake in an organ preparation of the hemisected rat skull.


METHODS
CGRP release from the cranial dura was quantified by a commercial enzyme-linked immunoassay. CGRP was depleted using repetitive challenges of capsaicin. After incubating the tissue with CGRP for 20 min and extensive washing, another capsaicin challenge was performed. Immunohistochemistry was used to visualize CGRP immunofluorescence in dural nerve fibres.


RESULTS
Capsaicin-induced CGRP release was attenuated by the transient receptor potential vanilloid receptor type I antagonist capsazepine or by Ca(2+)-free solutions. After the CGRP-depleted preparation had been exposed to exogenous CGRP, capsaicin-induced CGRP release was increased compared to the challenge just prior to incubation. CGRP uptake was not influenced by Ca(2+)-free solutions. Olcegepant and CGRP(8-37) (CGRP receptor antagonists) did not affect uptake of CGRP. However, a monoclonal CGRP-binding antibody decreased CGRP uptake significantly. Release of CGRP after incubation was attenuated by Ca(2+)-free solutions and by capsazepine. Immunohistochemical assays indicated a weak trend towards CGRP uptake in rat dura mater.


CONCLUSIONS
We have presented evidence for CGRP uptake in nerves and its re-release in rat dura mater. This may have implications for the pathophysiology and treatment of migraine.
Gupta
Saurabh
S
Department of Neurology, Glostrup Research Institute, Glostrup Hospital, Faculty of Health Science, University of Copenhagen, Glostrup, Copenhagen, Denmark.
Amrutkar
Dipak Vasantrao
DV
Mataji
Aydin
A
Salmasi
Hassan
H
Hay-Schmidt
Anders
A
Sheykhzade
Majid
M
Messlinger
Karl
K
Olesen
Jes
J
Jansen-Olesen
Inger
I
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism* / Q000494:pharmacology; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D002211:Capsaicin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004388:Dura Mater / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010879:Piperazines; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004151:Dipeptides; D010446:Peptide Fragments; D010879:Piperazines; D011799:Quinazolines; C058636:calcitonin gene-related peptide (8-37); D015740:Calcitonin Gene-Related Peptide; C071423:capsazepine; D002211:Capsaicin; D002118:Calcium; C406305:olcegepant
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