PMID- 8101490
OWN - NLM
STAT- MEDLINE
DCOM- 19930826
LR  - 20190624
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 245
IP  - 3
DP  - 1993 May 15
TI  - Isolation and characterization of histogranin, a natural peptide with NMDA 
      receptor antagonist activity.
PG  - 247-56
AB  - Histogranin, was co-purified with bombesin-like immunoreactive peptides from 
      bovine adrenal medulla. Its structure, 
      H-Met-Asn-Tyr-Ala-Leu-Lys-Gly-Gln-Gly-Arg-Thr-Leu-Tyr-Gly-Phe-COOH, was 
      determined by gas-phase Edman degradation. It was in accordance with its amino 
      acid composition and corresponded to a 15 amino acid fragment (fragment 86-100) 
      of histone H4 with substitutions in positions 1 (Val), 2 (Val) and 7 (Arg). The 
      peptide was synthesized by the solid-phase procedure and the synthetic product 
      was identical to the natural peptide as determined by its retention time on three 
      analytical high-performance liquid chromatography systems. An antibody was raised 
      against synthetic [Ser1]histogranin and used to monitor the presence of 
      histogranin in various rat tissues and subcellular fractions of bovine adrenal 
      medulla. In rats, immunoreactive histogranin was mainly concentrated in the 
      pituitary (5065 pmol/g) and the adrenal glands (268 pmol/g), but it was also 
      present in other tissues including the brain (1.6 pmol/g) and blood plasma (24 
      fmol/ml). A neuropeptide function for the adrenal peptide was suggested by its 
      relative high concentration in chromaffin granules (42 fmol/mg protein as 
      compared with 1 fmol/mg protein in cytosol) and its release from perfused bovine 
      adrenal glands. In rat brain membrane preparations, synthetic histogranin 
      displaced the binding of [3H]CGP 39653, a specific ligand of N-methyl-D-aspartate 
      (NMDA) receptor. The displacement curve was biphasic with IC50 of 0.6 and 3955 
      nM, representing 33% and 67% of the binding sites, respectively. 
      Intracerebroventricular (i.c.v.) injection of the peptide (5-100 nmol) in mice 
      produced a dose-dependent protection against NMDA (0.5-1.0 nmol) -induced 
      convulsions but not against 
      (R,S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA, 0.25-2.0 nmol), 
      kainate (0.25-0.75 nmol) and bicuculline (1-10 nmol)-induced convulsions. These 
      results suggest that histogranin may be an endogenous modulator of NMDA receptor 
      functions.
FAU - Lemaire, S
AU  - Lemaire S
AD  - Department of Pharmacology, Faculty of Medicine, University of Ottawa, Ontario, 
      Canada.
FAU - Shukla, V K
AU  - Shukla VK
FAU - Rogers, C
AU  - Rogers C
FAU - Ibrahim, I H
AU  - Ibrahim IH
FAU - Lapierre, C
AU  - Lapierre C
FAU - Parent, P
AU  - Parent P
FAU - Dumont, M
AU  - Dumont M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Amino Acids)
RN  - 0 (Proteins)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (Receptors, Phencyclidine)
RN  - 0 (Receptors, sigma)
RN  - 132472-31-2 (CGP 39653)
RN  - 150045-04-8 (histogranin)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - RP4A60D26L (Pentazocine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/analogs & derivatives/metabolism
MH  - Adrenal Medulla/*chemistry
MH  - Amino Acid Sequence
MH  - Amino Acids/analysis
MH  - Animals
MH  - Cattle
MH  - Chromatography, High Pressure Liquid
MH  - Dizocilpine Maleate/metabolism
MH  - Molecular Sequence Data
MH  - Pentazocine/metabolism
MH  - Proteins/chemistry/*isolation & purification/metabolism/pharmacology
MH  - Radioimmunoassay
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/metabolism
MH  - Receptors, Phencyclidine/drug effects
MH  - Receptors, sigma/drug effects
MH  - Tissue Distribution
EDAT- 1993/05/15 00:00
MHDA- 1993/05/15 00:01
CRDT- 1993/05/15 00:00
PHST- 1993/05/15 00:00 [pubmed]
PHST- 1993/05/15 00:01 [medline]
PHST- 1993/05/15 00:00 [entrez]
AID - 10.1016/0922-4106(93)90104-h [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1993 May 15;245(3):247-56. doi: 10.1016/0922-4106(93)90104-h.