Premium
Interaction of human adrenomedullin 13–52 with calcitonin gene‐related peptide receptors in the microvasculature of the rat and hamster
Author(s) -
Hall Judith M.,
Siney Lynn,
Lippton Howard,
Hyman Albert,
KangChang Jaw,
Brain Susan D.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb17180.x
Subject(s) - calcitonin gene related peptide , adrenomedullin , vasodilation , endocrinology , cheek pouch , medicine , calcitonin , hamster , receptor , chemistry , neuropeptide , biology
1 Adrenomedullin (ADM), a recently discovered circulating hypotensive peptide, shares limited sequence homology with the sensory nerve‐derived vasodilator, calcitonin gene‐related peptide (CGRP). This study compared the vasodilator effect of sequence 13–52 of human adrenomedullin (ADM 13–52 ) with that of human α CGRP (CGRP), in the microvasculature of the hamster cheek pouch and rat skin in vivo . 2 Single arterioles (20–40 μm diameter) in the hamster cheek pouch were visualised by intravital microscopy and video recording, and measured by image analysis. Both ADM 13–52 (1 pmol–0.4 nmol) and CGRP (0.1 pmol–1 nmol) evoked dose‐related increases in the diameter of preconstricted arterioles ( n = 6). ADM 13–52 (ED 50 14 pmol) was 20 fold less active than CGRP (ED 50 0.71 pmol). The kinetics of onset and decline of vasodilator responses to both peptides were similar, with vasodilator responses to both peptides reaching a maximum at ca . 2 min, and reversing after 10–15 min ( n = 5–7). The submaximal increase in blood flow evoked by ADM 13–52 was significantly inhibited ( P < 0.05; n = 6) by the CGRP 1 receptor antagonist, CGRP 8–37 , at a dose (300 nmol kg −1 , i.v.) that we have previously shown to inhibit significantly equivalent vasodilator responses to CGRP in this preparation. 3 In experiments measuring changes in local blood flow in rat skin by a 133 xenon clearance technique, intradermal injection of both ADM 13–52 (3–300 pmol) and CGRP (0.1–30 pmol) evoked dose‐related increases in local blood flow. ADM 13–52 (ED 50 27 pmol) was 17 fold less potent than CGRP (ED 50 1.6 pmol) ( n = 6). The submaximal increase in blood flow evoked by both peptides was significantly inhibited ( P < 0.02; n = 5) by CGRP 837 (100 nmol kg −1 , i.v.). 4 We conclude that ADM 13–52 is a potent vasodilator in the microvasculature of the hamster and rat in vivo . It mediates its vasodilator effect by arteriolar dilatation and this effect is due, at least in part, to the stimulation of CGRP 1 receptors.