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Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain
Author(s) -
Asano T.,
Ikegaki I.,
Satoh S.,
Mochizuki D.,
Hidaka H.,
Suzuki Y.,
Shibuya M.,
Sugita K.
Publication year - 1991
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/j.1476-5381.1991.tb12355.x
Subject(s) - gerbil , nicardipine , medicine , calcium , pharmacology , contraction (grammar) , calcium in biology , ischemia , anesthesia
1 The brain cytoprotective effects of a putative calcium‐associated protein kinase inhibitor, HA1077, as well as a calcium entry blocker nicardipine were evaluated in models of cerebral ischaemia in Mongolian gerbils. Morphological changes characterizing delayed neuronal death of selectively vulnerable CA 1 pyramidal neurones in the hippocampus of the Mongolian gerbil brain occurred 7 days after transient bilateral occlusion of the common carotid arteries. 2 A single injection of HA1077 (1 and 3 mg kg −1 , i.p.) 5 min after the occlusion led to a dose‐dependent protection of the CA 1 neurones. Repeated administrations of HA1077 (1 and 3 mg kg −1 , i.p., twice daily for 7 days post‐ischaemia) revealed an increase in the number of normal cells, compared to findings with a single administration. 3 In contrast to HA1077, nicardipine (0.3 and 1 mg kg −1 , i.p.) did not reduce neuronal degeneration. 4 HA1077 did not interact with the ion channel within which MK‐801 binds, as determined by receptor binding. 5 The calcium ionophore, A23187, caused a tonic contraction in canine cerebral arterial strips. HA1077, but not nicardipine, relaxed the A23187‐induced contraction, concentration‐dependently. 6 These results suggest that blockade of the intracellular actions of calcium may provide protection against ischaemic damage in the brain.