title: Brain RVD-haemopressin, a haemoglobin-derived peptide, inhibits bombesin-induced central activation of adrenomedullary outflow in the rat.
abstract: OBJECTIVE
  Haemopressin and RVD-haemopressin, derived from the haemoglobin α-chain, are bioactive peptides found in brain and are ligands for cannabinoid CB1 receptors. Activation of brain CB1 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
  
  
  METHODS
  Anaesthetised male Wistar 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.
  
  
  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 (CB1 receptor agonist) but not after pretreatment with haemopressin (CB1 receptor inverse agonist). Bombesin activated haemoglobin α-positive spinally projecting neurons in the PVN.
  
  
  CONCLUSIONS
  The haemoglobin-derived peptide RVD-haemopressin in the brain plays an inhibitory role in bombesin-induced activation of central adrenomedullary outflow via brain CB1 receptors in the rat. These findings provide basic information for the therapeutic use of haemoglobin-derived peptides in the modulation of central adrenomedullary outflow.
authors.affiliation: Department of Pharmacology, Kochi University School of Medicine, Nankoku, Japan.
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yanagita
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nemoto
authors.forename: Kumiko
authors.initials: K
authors.lastname: Nakamura
authors.forename: Keisuke
authors.initials: K
authors.lastname: Taniuchi
authors.forename: Fotios
authors.initials: F
authors.lastname: Dimitriadis
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Yokotani
authors.forename: Motoaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000313:Adrenal Medulla / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D000818:Animals; D001839:Bombesin / Q000008:administration & dosage / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054314:Drug Inverse Agonism; D004837:Epinephrine / Q000097:blood* / Q000378:metabolism; D006454:Hemoglobins / Q000008:administration & dosage / Q000494:pharmacology*; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000097:blood* / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000378:metabolism; D013127:Spinal Nerves / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
chemical_list: D063386:Cannabinoid Receptor Agonists; C543264:Cnr1 protein, rat; D006454:Hemoglobins; D010446:Peptide Fragments; C000590773:RVD-hemopressin, human; D043884:Receptor, Cannabinoid, CB1; C473218:hemopressin; D001839:Bombesin; D009638:Norepinephrine; D004837:Epinephrine
keywords: bombesin; brain; cannabinoid CB1 receptor; central adrenomedullary outflow; haemoglobin-derived peptides