Calcitonin-gene related peptide induces a long lasting vasodilation of the spiral modiolar artery
Project management at the University of Würzburg:
Several inner ear diseases are said to be related to microcirculatory disorders. Knowledge about vasodilatory mechanisms might provide the idea for a reasonable drug therapy of inner ear disorders. The aim of the present study was to localize calcitonin gene-related peptide (CGRP) in the gerbil spiral modiolar artery (SMA) and to identify receptors and signal transduction.
Vascular diameter and intracellular calcium [Ca2+]i were measured by vidoemikroskopie and microfluometry. CGRP was localized by immunohistochemistry and CGRP receptor mRNA was identified by RT-PCR. The SMA was preconstricted with 10nM endothelin-1.
CGRP and forskolin caused a vasodilation of the SMA (EC50 = 0.1 nM and 0.3 μM) and caused an increase of intracellular cAMP as well as a transient decrease of [Ca2+]i. The induced vasodilation remained stable despite a normalized [Ca2+]i . The CGRP induced vasodilation was inhibited by the receptor antagonist CGRP8-37 (KDB = 2.1 μM). The K+-channel blocker iberiotoxin and glibenclamide reduced the CGRP and forskolin induced vasodilation but did not have an effect on an already existing vasodilation.
The results indicate that CGRP is present in perivascular nerves of the gerbil SMA and induces and maintains a vasodilation via different mechanisms. The mechanism of a potential calcium desensitisation induced by CGRP is still to be investigated.
Projekt period: from 02.2000 to 01.2002
Sonstige öffentliche Mittel ( NIH Grant )