CGRP receptors in the gerbil spiral modiolar artery mediate a sustained vasodilation via a transient cAMP-mediated...

Area of Science:

• Vascular physiology
• Neuroendocrinology
• Otolaryngology

Background:

• Cochlear blood flow is crucial for inner ear health, and its alterations may contribute to hearing loss and tinnitus.
• The spiral modiolar artery (SMA) is the primary blood supply to the cochlea, making its regulation vital.

Purpose of the Study:

• To investigate the localization of calcitonin gene-related peptide (CGRP) in the gerbil SMA.
• To identify CGRP receptors and elucidate the signaling pathways involved in CGRP-mediated vasodilation in the SMA.

Main Methods:

• Immunocytochemistry was used to localize CGRP in perivascular nerves.
• Videomicroscopy and fluo-4-microfluorometry simultaneously measured vascular diameter and cytosolic Ca2+ concentration ([Ca2+]i).
• RT-PCR identified Calcitonin receptor-like receptor (CRLR) mRNA in the vascular wall.
• Pharmacological agents (endothelin-1, CGRP, forskolin, dibutyryl-cAMP, CGRP8-37, iberiotoxin, glibenclamide) were used to assess vasodilation and signaling.

Main Results:

• CGRP was localized in perivascular nerves of the SMA.
• CGRP, forskolin, and dibutyryl-cAMP induced significant vasodilation.
• CGRP-induced vasodilation involved increased cAMP production, a transient decrease in [Ca2+]i, and activation of specific K+ channels.
• The CGRP-induced vasodilation was antagonized by CGRP8-37 and partially affected by K+ channel blockers.

Conclusions:

• CGRP is a potent vasodilator in the gerbil SMA, acting via perivascular nerves.
• The vasodilation mechanism involves cAMP elevation, transient [Ca2+]i reduction, and activation of iberiotoxin-sensitive BK and glibenclamide-sensitive KATP channels.
• These findings provide insights into the role of CGRP in regulating cochlear blood flow and potential therapeutic targets for inner ear disorders.