Domoic Acid Inhibits Adenylate Cyclase Activity in Rat Brain Membranes

Overview

Journal Mol Cell Biochem

Publisher Springer

Specialty Biochemistry

Date 1994 Jul 27

PMID 7845363

Citations 2

Authors

M S Nijjar

B Grimmelt

Affiliations

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Abstract

Adenylate cyclase activity measured by the formation of cyclic AMP in rat brain membranes was inhibited by a shellfish toxin, domoic acid (DOM). The inhibition of enzyme was dependent on DOM concentration, but about 50% of enzyme activity was resistant to DOM-induced inhibition. Rat brain supernatant resulting from 105,000 x g centrifugation for 60 min, stimulated adenylate cyclase activity in membranes. Domoic acid abolished the supernatant-stimulated adenylate cyclase activity. The brain supernatant contains factors which modulate adenylate cyclase activity in membranes. The stimulatory factors include calcium, calmodulin, and GTP. In view of these findings, we examined the role of calcium and calmodulin in DOM-induced inhibition of adenylate cyclase in brain membranes. Calcium stimulated adenylate cyclase activity in membranes, and further addition of calmodulin potentiated calcium-stimulated enzyme activity in a concentration dependent manner. Calmodulin also stimulated adenylate cyclase activity, but further addition of calcium did not potentiate calmodulin-stimulated enzyme activity. These results show that the rat brain membranes contain endogenous calcium and calmodulin which stimulate adenylate cyclase activity. However, calmodulin appears to be present in membranes in sub-optimal concentration for adenylate cyclase activation, whereas calcium is present at saturating concentration. Adenylate cyclase activity diminished as DOM concentration was increased, reaching a nadir at about 1 mM. Addition of calcium restored DOM-inhibited adenylate cyclase activity to the control level. Similarly, EGTA also inhibited adenylate cyclase activity in brain membranes in a concentration dependent manner, and addition of calcium restored EGTA-inhibited enzyme activity to above control level.(ABSTRACT TRUNCATED AT 250 WORDS)

Citing Articles

Effect of pH on domoic acid toxicity in mice.

Nijjar M, Madhyastha M Mol Cell Biochem. 1997; 167(1-2):179-85.

PMID: 9059995 DOI: 10.1023/a:1006862311940.

Domoic acid inhibits adenylate cyclase activity in rat brain membranes.

Nijjar M, Grimmelt B Mol Cell Biochem. 1994; 136(2):105-11.

PMID: 7845363 DOI: 10.1007/BF00926069.

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