Activation of 5-HT1A receptors inhibits carbachol-stimulated inositol 1,4,5-trisphosphate mass accumulation in the rodent hippocampus.
We have previously demonstrated that 5-HT1A receptor 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 IP3 and this response was partially inhibited by 8-OH-DPAT with a potency compatible with the affinity of this agonist for 5-HT1A receptors. 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 PIP2 hydrolysis in hippocampal membranes, suggesting that this compound induces long lasting changes of muscarinic receptors and/or their effector mechanism by an indirect action.
Minisclou
C
C
Synthelabo Recherche (LERS), Department of Preclinical Research, Bagneux, France.
Benavides
J
J
Claustre
Y
Y
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013268:Stimulation, Chemical
D017366:Serotonin Receptor Agonists; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol