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Brain RVD ‐haemopressin, a haemoglobin‐derived peptide, inhibits bombesin‐induced central activation of adrenomedullary outflow in the rat
Author(s) -
Tanaka Kenjiro,
Shimizu Takahiro,
Yanagita Toshihiko,
Nemoto Takayuki,
Nakamura Kumiko,
Taniuchi Keisuke,
Dimitriadis Fotios,
Yokotani Kunihiko,
Saito Motoaki
Publication year - 2014
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/bph.12471
Subject(s) - bombesin , medicine , endocrinology , receptor , chemistry , agonist , adrenal medulla , chromaffin cell , biology , catecholamine , neuropeptide
Background and Purpose Haemopressin and RVD ‐haemopressin, derived from the haemoglobin α‐chain, are bioactive peptides found in brain and are ligands for cannabinoid CB 1 receptors. Activation of brain CB 1 receptors inhibited the secretion of adrenal catecholamines (noradrenaline and adrenaline) induced by i.c.v. bombesin in the rat. Here, we investigated the effects of two haemoglobin‐derived peptides on this bombesin‐induced response Experimental Approach Anaesthetised male W istar rats were pretreated with either haemoglobin‐derived peptide, given i.c.v., 30 min before i.c.v. bombesin and plasma catecholamines were subsequently measured electrochemically after HPLC. Direct effects of bombesin on secretion of adrenal catecholamines were examined using bovine adrenal chromaffin cells. Furthermore, activation of haemoglobin α‐positive spinally projecting neurons in the rat hypothalamic paraventricular nucleus ( PVN , a regulatory centre of central adrenomedullary outflow) after i.c.v. bombesin was assessed by immunohistochemical techniques. Key Results Bombesin given i.c.v. dose‐dependently elevated plasma catecholamines whereas incubation with bombesin had no effect on spontaneous and nicotine‐induced secretion of catecholamines from chromaffin cells. The bombesin‐induced increase in catecholamines was inhibited by pretreatment with i.c.v. RVD ‐haemopressin ( CB 1 receptor agonist) but not after pretreatment with haemopressin ( CB 1 receptor inverse agonist). Bombesin activated haemoglobin α‐positive spinally projecting neurons in the PVN . Conclusions and Implications The haemoglobin‐derived peptide RVD ‐haemopressin in the brain plays an inhibitory role in bombesin‐induced activation of central adrenomedullary outflow via brain CB 1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin‐derived peptides in the modulation of central adrenomedullary outflow.