CHARACTERIZATION OF BINDING-SITES AND EFFECTS OF CALCITONIN-GENE-RELATED PEPTIDE (CGRP) AND CGRP-8-37 ON REGIONAL BLOOD-FLOW IN RABBIT SALIVARY-GLANDS

Calcitonin gene-related peptide (CGRP) is a neuropeptide present in ne rve fibres of salivary glands in several species, including man. One o f the major targets of these nerve fibres are blood vessels of the gla nds. The presence and distribution of specific binding sites for CGRP in the rabbit major salivary glands was here investigated autoradiogra phically. In order to determine the physiological role of CGRP, region al blood flow was measured after intravenous (i.v.) or intra-arterial (i.a.) administration of CGRP or the antagonist CGRP 8-37, using a mic rosphere technique. Specific binding sites for CGRP were found in the parotid, submandibular and sublingual glands, distributed mainly in th e muscular and endothelial layers of the blood vessel walls. CGRP inje cted i.a. (10 pmol/kg) caused a significant increase in regional blood flow in all major salivary glands. However, i.v. infusion of CGRP (12 0 pmol/kg) decreased regional blood flow in the parotid and sublingual glands, due to a general decrease in peripheral resistance and redist ribution 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 g lands are localized in vascular elements. The physiological data show that CGRP acts as a vasodilator in the major salivary glands of the ra bbit in vivo, and that the effect of CGRP is inhibited by the CGRP ant agonist CGRP 8-37.