Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1991 Aug;103(4):1935–1938. doi: 10.1111/j.1476-5381.1991.tb12355.x

Blockade of intracellular actions of calcium may protect against ischaemic damage to the gerbil brain.

T Asano 1, I Ikegaki 1, S Satoh 1, D Mochizuki 1, H Hidaka 1, Y Suzuki 1, M Shibuya 1, K Sugita 1
PMCID: PMC1908195  PMID: 1912980

Abstract

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 CA1 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 CA1 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.

Full text

PDF
1935

Images in this article

1936Figure 1
on p.1936

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alps B. J., Calder C., Hass W. K., Wilson A. D. Comparative protective effects of nicardipine, flunarizine, lidoflazine and nimodipine against ischaemic injury in the hippocampus of the Mongolian gerbil. Br J Pharmacol. 1988 Apr;93(4):877–883. doi: 10.1111/j.1476-5381.1988.tb11475.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Asano T., Ikegaki I., Satoh S., Suzuki Y., Shibuya M., Takayasu M., Hidaka H. Mechanism of action of a novel antivasospasm drug, HA1077. J Pharmacol Exp Ther. 1987 Jun;241(3):1033–1040. [PubMed] [Google Scholar]
  3. Asano T., Suzuki T., Tsuchiya M., Satoh S., Ikegaki I., Shibuya M., Suzuki Y., Hidaka H. Vasodilator actions of HA1077 in vitro and in vivo putatively mediated by the inhibition of protein kinase. Br J Pharmacol. 1989 Dec;98(4):1091–1100. doi: 10.1111/j.1476-5381.1989.tb12652.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DeLeo J., Toth L., Schubert P., Rudolphi K., Kreutzberg G. W. Ischemia-induced neuronal cell death, calcium accumulation, and glial response in the hippocampus of the Mongolian gerbil and protection by propentofylline (HWA 285). J Cereb Blood Flow Metab. 1987 Dec;7(6):745–751. doi: 10.1038/jcbfm.1987.129. [DOI] [PubMed] [Google Scholar]
  5. Fleckenstein A. Specific pharmacology of calcium in myocardium, cardiac pacemakers, and vascular smooth muscle. Annu Rev Pharmacol Toxicol. 1977;17:149–166. doi: 10.1146/annurev.pa.17.040177.001053. [DOI] [PubMed] [Google Scholar]
  6. Izumiyama K., Kogure K. Prevention of delayed neuronal death in gerbil hippocampus by ion channel blockers. Stroke. 1988 Aug;19(8):1003–1007. doi: 10.1161/01.str.19.8.1003. [DOI] [PubMed] [Google Scholar]
  7. Kirino T. Delayed neuronal death in the gerbil hippocampus following ischemia. Brain Res. 1982 May 6;239(1):57–69. doi: 10.1016/0006-8993(82)90833-2. [DOI] [PubMed] [Google Scholar]
  8. Pulsinelli W. A., Brierley J. B., Plum F. Temporal profile of neuronal damage in a model of transient forebrain ischemia. Ann Neurol. 1982 May;11(5):491–498. doi: 10.1002/ana.410110509. [DOI] [PubMed] [Google Scholar]
  9. Sakamoto N., Kogure K., Kato H., Ohtomo H. Disturbed Ca2+ homeostasis in the gerbil hippocampus following brief transient ischemia. Brain Res. 1986 Feb 5;364(2):372–376. doi: 10.1016/0006-8993(86)90850-4. [DOI] [PubMed] [Google Scholar]
  10. Sasaki Y., Sasaki Y., Kanno K., Hidaka H. Disorganization by calcium antagonists of actin microfilament in aortic smooth muscle cells. Am J Physiol. 1987 Jul;253(1 Pt 1):C71–C78. doi: 10.1152/ajpcell.1987.253.1.C71. [DOI] [PubMed] [Google Scholar]
  11. Schaffer S. W., Safer B., Scarpa A., Williamson J. R. Mode of action of the calcium ionophores X-537A and A23187 on cardiac contractility. Biochem Pharmacol. 1974 May 1;23(11):1609–1617. doi: 10.1016/0006-2952(74)90373-6. [DOI] [PubMed] [Google Scholar]
  12. Siesjö B. K. Cell damage in the brain: a speculative synthesis. J Cereb Blood Flow Metab. 1981;1(2):155–185. doi: 10.1038/jcbfm.1981.18. [DOI] [PubMed] [Google Scholar]
  13. Steen P. A., Newberg L. A., Milde J. H., Michenfelder J. D. Cerebral blood flow and neurologic outcome when nimodipine is given after complete cerebral ischemia in the dog. J Cereb Blood Flow Metab. 1984 Mar;4(1):82–87. doi: 10.1038/jcbfm.1984.10. [DOI] [PubMed] [Google Scholar]
  14. Yoshida S., Inoh S., Asano T., Sano K., Kubota M., Shimazaki H., Ueta N. Effect of transient ischemia on free fatty acids and phospholipids in the gerbil brain. Lipid peroxidation as a possible cause of postischemic injury. J Neurosurg. 1980 Sep;53(3):323–331. doi: 10.3171/jns.1980.53.3.0323. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES