TY - JOUR
T1 - Evidence for CGRP re-uptake in rat dura mater encephali
AU - Gupta, Saurabh
AU - Amrutkar, Dipak Vasantrao
AU - Mataji, Aydin
AU - Salmasi, Hassan
AU - Hay-Schmidt, Anders
AU - Sheykhzade, Majid
AU - Messlinger, Karl
AU - Olsen, Jes
AU - Jansen-Olesen, Inger
N1 - © 2010 The Authors. British Journal of Pharmacology © 2010 The British Pharmacological Society.
PY - 2010/12
Y1 - 2010/12
N2 - BACKGROUND AND PURPOSE 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.EXPERIMENTAL APPROACH 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.KEY 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.CONCLUSION AND IMPLICATIONS 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.
AB - BACKGROUND AND PURPOSE 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.EXPERIMENTAL APPROACH 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.KEY 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.CONCLUSION AND IMPLICATIONS 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.
KW - Former Faculty of Pharmaceutical Sciences
U2 - 10.1111/j.1476-5381.2010.01012.x
DO - 10.1111/j.1476-5381.2010.01012.x
M3 - Journal article
SN - 0007-1188
VL - 161
SP - 1885
EP - 1898
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 8
ER -