The neuropeptide calcitonin gene-related peptide (CGRP) from the trigeminal ganglion has been established as a key player in the pathogenesis of migraine. In this study, we provide evidence that the responsiveness of neuronal CGRP receptors is strongly enhanced in vitro and in vivo by expression of human receptor activity-modifying protein-1 (hRAMP1), an obligatory subunit of the CGRP receptor....

Somatostatin messenger RNA in the antrum and corpus of rat stomach was quantified by Northern and slot blotting using a probe generated by the polymerase chain reaction. Fasting for 48 h enhanced the abundance of somatostatin mRNA in the pyloric antral region, but not in the acid-secreting region of the stomach. In fasted rats, somatostatin mRNA in antrum, but not corpus, was decreased by inhib...

Calcitonin gene-related peptide (CGRP) receptors are classified into CGRP subtype 1 (CGRP(1)) and CGRP subtype 2 (CGRP(2)) based on the affinity of the antagonist, human alpha (halpha)-CGRP(8-37). halpha-CGRP(8-37) antagonizes CGRP(1) receptor-mediated responses with high affinity (K(B) < 100 nM) and antagonizes CGRP(2) receptor-mediated responses with low affinity (K(B) > 1 microM). CGRP(2) re...

The CGRP (calcitonin gene-related peptide) receptor is a family B GPCR (G-protein-coupled receptor). It consists of a GPCR, CLR (calcitonin receptor-like receptor) and an accessory protein, RAMP1 (receptor activity-modifying protein 1). RAMP1 is needed for CGRP binding and also cell-surface expression of CLR. There have been few systematic studies of the ECLs (extracellular loops) of family B G...

Introduction Cortical spreading depression (CSD) is believed to promote migraine headache by enhancing the activity and mechanosensitivity of trigeminal intracranial meningeal afferents. One putative mechanism underlying this afferent response involves an acute excitation of meningeal afferents by cortical efflux of K+ and the ensuing antidromic release of proinflammatory sensory neuropeptides,...

Intermedin (IMD) is a member of calcitonin/calcitonin gene-related peptide family, which shares the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMPs). This study investigated the effects of IMD in paraventricular nucleus (PVN) on renal sympathetic nerve activity and mean arterial pressure and its downstream mechanism in hyper...

In the guinea pig distal colon, calcitonin gene-related peptide (CGRP, 0.1-30 nM) produced a concentration-dependent inhibition in electrically-evoked nonadrenergic noncholinergic (NANC) contractions and exogenous substance P-induced contractions. Both the inhibitory actions of CGRP were insensitive to human CGRP(8-37) (1-3 microM), a CGRP1 receptor antagonist. These results indicate that in th...