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Effects of estrogen on intracellular signaling pathways linked to activation of muscarinic acetylcholine receptors and on acetylcholinesterase activity in rat hippocampus.

Pereira RT, Porto CS, Godinho RO, Abdalla FM

Laboratory of Pharmacology, Instituto Butantan, Av. Vital Brazil 1500, São Paulo, SP 05503-900, Brazil.

The aim of the present study was to investigate the effects of estrogen lack and estrogen replacement on the production of total [3H]inositol phosphate ([3H]IP) induced by the activation of muscarinic acetylcholine receptors (mAChRs) and on the mechanisms for inactivation of acetylcholine. Hippocampi were obtained from rats in proestrus (PE), ovariectomized for 15 days (C15), ovariectomized for 15 days and then treated with 17beta-estradiol for 7 days (E7) and ovariectomized and immediately treated with 17beta-estradiol for 21 days (E21). Ovariectomy did not change the basal level of total [3H]IP in the hippocampus. 17beta-Estradiol replacement (E7 and E21) reduced the basal level of total [3H]IP. In all experimental groups, carbachol (CCh) caused a concentration-dependent rise in total [3H]IP. The maximum effect was reached with 10(-4) M CCh. The response to 10(-4) M CCh in the hippocampi from C15 and E7 rats was twofold higher than in hippocampi from PE and E21 animals and was blocked by pirenzepine, but not by methoctramine. Ovariectomy or 17beta-estradiol treatment for 7 days did not change neither the total acetylcholinesterase (AChE) activity nor the relative amount of mono- and dimeric G1/G2 and tetrameric G4 globular forms. Conversely, hormonal treatment for 21 days induced an increase in AChE activity of G1/G2 and G4 forms, indicating that 17beta-estradiol stimulates both synthesis and assembly of AChE molecular forms. The present results suggest that the duration and/or a critical period with regard to the initiation of estrogen therapy are important to regulate the function of mAChRs and AChE activity in female rat hippocampus.

Published 18 April 2008 in Biochem Pharmacol, 75(9): 1827-34.
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