Aging alters in a region-specific manner serotonin transporter sites and 5-HT(1A) receptor-G protein interactions in hamster brain.
Key proteins regulating serotonergic activity, specifically the serotonin transporter and 5-HT(1A) receptor, were examined in the midbrain raphe nuclei of young (3-4 months) and old (17-19 months) hamsters (N=7-10/group). An age-related decrease in the maximal density of serotonin transporter sites labelled with [(3)H]paroxetine (fmol/mg protein, Old: 396+/-13; Young: 487+/-27) was observed in the dorsal raphe nucleus (DRN) but not the median raphe nucleus (MRN), without affecting the affinity of [(3)H]paroxetine. In the DRN and MRN, the stimulation of [(35)S]GTP gamma S binding by the 5-HT(1A) receptor agonist 8-OH-DPAT, or the number of 5-HT(1A) receptor sites labeled with [(3)H] MPPF, was not different in old versus young animals. Thus in the DRN, aging decreased serotonin transporter sites without changing 5-HT(1A) receptor activation of G proteins or 5-HT(1A) receptor density. In the CA(1) region of hippocampus, 8-OH-DPAT-stimulated [(35)S]GTP gamma S binding was increased in the older animals (% above basal, Old: 141+/-21; Young: 81+/-17) without changing specific [(3)H] MPPF binding sites, suggesting that the capacity of 5-HT(1A) receptors to activate G proteins is enhanced. Aging also appears to enhance this capacity in the dentate gyrus, because this region exhibited a constant level of 8-OH-DPAT-stimulated [(35)S]GTP gamma S binding in spite of an age-related decrease in the number of [(3)H] MPPF binding sites (fmol/mg protein, Old: 203+/-21; Young: 429+/-51).
Duncan
Marilyn J
MJ
Department of Anatomy and Neurobiology, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536-0298, USA. mjdunc0@pop.uky.edu
Hensler
Julie G
JG
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D006224:Cricetinae; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives* / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins; D008647:Mesocricetus; D009419:Nerve Tissue Proteins; D017374:Paroxetine / Q000378:metabolism / Q000494:pharmacology; D010879:Piperazines / Q000378:metabolism / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000378:metabolism / Q000494:pharmacology
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D002352:Carrier Proteins; D019204:GTP-Binding Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C034882:guanosine 5'-O-(1-thiotriphosphate); C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide