Histaminergic H2 action protects hippocampal CA1 neurons by prolonging the onset of the anoxic depolarization in gerbils.
The central histaminergic action on ischemia-induced neuronal damage was examined by evaluating the histological outcome and the direct current (DC) potential shift in the hippocampal CA1 region in gerbils. An intracerebroventricular administration of histamine (10-100 nmol) improved the delayed ischemic damage in hippocampal CA1 pyramidal cells produced by 3 min of transient forebrain ischemia. A high dose (75 nmol) of mepyramine, an H1 antagonist, aggravated ischemia-induced neuronal damage, but not a low dose (0.75 nmol). Administration of cimetidine (4 nmol) and ranitidine (3 nmol), H2 antagonists, aggravated the neuronal damage. An injection of histamine (100 nmol) prolonged the onset time of the ischemia-induced sudden shift in the extracellular DC potential (anoxic depolarization; AD) to 133% of that in control animals. Administration of mepyramine (75 nmol) did not markedly change the AD, whereas injections of cimetidine (40 nmol) and ranitidine (3 nmol) reduced the onset latency to 47 and 45%, respectively. These findings suggest that the central H2 action serves to protect neurons by delaying the onset of AD in gerbils.
Fujitani
T
T
Department of Anesthesiology, Ehime University School of Medicine, Japan.
Adachi
N
N
Nagaro
T
T
Miyazaki
H
H
Nakamura
Y
Y
Kataoka
K
K
Arai
T
T
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology*; D006632:Histamine / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D011970:Receptors, Histamine H2 / Q000502:physiology*
D018696:Neuroprotective Agents; D011970:Receptors, Histamine H2; D006632:Histamine