Activation of 5-HT1Areceptors inhibits carbachol-stimulated inositol 1,4,5-trisphosphate mass accumulation in the rodent hippocampus

摘要

We have previously demonstrated that 5-HT1Areceptor agonists partially prevent the stimulation by carbachol of 3H-phosphoinositide hydrolysis in immature rat hippocampal slices. This negative modulation has been investigated further by measuring, using a radioreceptor assay, the mass accumulation of IP3. In hippocampal slices from developing rats and in hippocampal neurons, carbachol enhanced the accumulation of IP3and this response was partially inhibited by 8-OH-DPAT with a potency compatible with the affinity of this agonist for 5-HT1Areceptors. The inhibition of the carbachol response by 8-OH-DPAT was non-competitive in nature and 8-OH-DPAT did not affect the inhibitory potency of pirenzepine. The inhibitory effect of 8-OH-DPAT was maintained after washing the slices preincubated with this compound but was not observed on the carbachol-stimulated PIP2hydrolysis in hippocampal membranes, suggesting that this compound induces long lasting changes of nuscarinic receptors and/or their effector mechanism by an indirect action.