dizocilpine-maleate and phorbol-12-13-didecanoate

We investigated the effects of age and nafidrofuryl oxalate (Naftidrofuryl), a 5-HT2 antagonist, on neurotransmission and transduction systems in the gerbil hippocampus using quantitative autoradiography. [3H]Quinuclidinyl benzilate (QNB), [3H]cyclohexyl-adenosine (CHA), [3H]MK-801, and [3H]muscimol were used to label muscarinic acetylcholine, adenosine A1, N-methyl-D-aspartate (NMDA), and gamma-aminobutyric acid-A (GABAA) receptors, respectively. [3H]PN200-110 labeled L-type Ca2+ channels. [3H]Forskolin, [3H]cyclic adenosine monophosphate (cAMP), [3H]phorbol 12,13-dibutyrate (PDBu), and [3H]inositol 1,4,5-triphosphate (IP3) were used to label adenylate cyclase, cAMP-dependent protein kinase, protein kinase C (PKC), and IP3 receptors, respectively. Approximately 20% reductions in [3H]QNB, [3H]forskolin, and [3H]PDBu binding were observed in the hippocampus of 9-month-old gerbils in comparison with 5-week-old gerbils. Treatment with Naftidrofuryl (10 mg/kg, i.p., once a day for 7 days) ameliorated these reductions. No changes were found in [3H]CHA, [3H]MK-801, [3H]muscimol, [3H]PN200-110, [3H]cAMP, and [3H]IP3 binding. The results suggest that Naftidrofuryl may have beneficial effects on the age-related alterations in signal transmission and transduction systems in the brain. Because the acetylcholine system, adenylate cyclase, and PKC are considered to be involved in learning and memory processes, the result may have clinical implications.

Topics: Adenosine; Adenylyl Cyclases; Animals; Autoradiography; Colforsin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dizocilpine Maleate; Gerbillinae; Hippocampus; Inositol 1,4,5-Trisphosphate; Isradipine; Male; Muscimol; Nafronyl; Phorbol Esters; Protein Kinase C; Quinuclidinyl Benzilate; Sensory Receptor Cells; Serotonin Antagonists; Signal Transduction; Synaptic Transmission; Tritium