Characterization of binding sites and effects of calcitonin gene-related peptide (CGRP) and CGRP 8–37 on regional blood flow in rabbit salivary glands

Abstract

Calcitonin gene-related peptide (CGRP) is a neuropeptide present in nerve fibres of salivary glands in several species, including man. One of the major targets of these nerve fibres are blood vessels of the glands. The presence and distribution of specific binding sites for CGRP in the rabbit major salivary glands was here investigated autoradiographically. In order to determine the physiological role of CGRP, regional blood flow was measured after intravenous (i.v.) or intra-arterial (i.a.) administration of CGRP or the antagonist CGRP 8–37, using a microsphere technique. Specific binding sites for CGRP were found in the parotid, submandibular and sublingual glands, distributed mainly in the muscular and endothelial layers of the blood vessel walls. CGRP injected i.a. (10 pmol/kg) caused a significant increase in regional blood flow in all major salivary glands. However, i.v. infusion of CGRP (120 pmol/kg) decreased regional blood flow in the parotid and sublingual glands, due to a general decrease in peripheral resistance and redistribution of peripheral blood flow. CGRP 8–37 given i.a. together with CGRP significantly inhibited the blood-flow increase by CGRP alone. It is concluded that most of the CGRP receptors in the rabbit salivary glands are localized in vascular elements. The physiological data show that CGRP acts as a vasodilator in the major salivary glands of the rabbit in vivo, and that the effect of CGRP is inhibited by the CGRP antagonist CGRP 8–37.