Histaminergic H(2) blockade facilitates ischemic release of dopamine in gerbil striatum.
The blockade of central histaminergic H(2) receptors has been reported to aggravate ischemic neuronal damage. Since excess release of excitatory neurotransmitters is closely related to ischemic neuronal damage, the effects of ranitidine on ischemic release of dopamine were investigated in gerbil striatum. Changes in the extracellular concentration of dopamine produced by transient forebrain ischemia for 4 min were investigated by a microdialysis procedure, and the effect of intracerebroventricular administration of ranitidine (10 nmol) was evaluated. The histologic outcome was examined 7 days after ischemia by light microscopy. Forebrain ischemia produced a marked increase in the dopamine concentration in dialysates, and the level returned to the basal level after reperfusion. The preischemic administration of ranitidine enhanced the increase in the dopamine level during ischemia, and the peak value in the ranitidine group was 203% of that in the saline group. The histologic outcome was aggravated by the ranitidine treatment in the striatum, although aggravation was not observed in the cerebral cortex. The facilitation of the ischemic release of dopamine may be a contributing factor in the aggravation of ischemic damage by H(2) blockade.
Adachi
Naoto
N
Department of Anesthesiology and Resuscitology, Ehime University School of Medicine, Shitsukawa, Shigenobu-cho, Onsen-gun, Ehime, Japan. nadachi@m.ehime-u.ac.jp
Terao
Kin'ya
K
Otsuka
Ryu
R
Arai
Tatsuru
T
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005849:Gerbillinae; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*
D006635:Histamine H2 Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D011899:Ranitidine; D004298:Dopamine; D006719:Homovanillic Acid