[Multiple [3H]8-hydroxy-2-(di-n-propylamino)-tetralin binding sites in rat brain: modulation by GTP and cations].
[3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) is thought to label a single population of serotonin (5-HT)1A receptor, but some reports implicate multiple binding sites exist. In addition, while 5-HT1A receptor activates or inhibits adenylate cyclase, 5-HT1A receptor high and low affinity states are not reported. In this experiment, we found that [3H]8-OH-DPAT had multiple binding sites, which contained 5-HT1A receptor high and low affinity states, in rat brain membranes. [3H]8-OH-DPAT saturation binding experiment revealed high and low affinity binding sites existed. High affinity binding site was dense in hippocampus and sparse in striatum. 5-HT agonist and antagonist biphasically displaced [3H]8-OH-DPAT binding in frontocortical, hippocampal, and striatal membranes. These drugs potently displaced high affinity [3H]8-OH-DPAT binding, but clomipramine (5-HT reuptake inhibitor) potently displaced low affinity binding. High affinity [3H]8-OH-DPAT binding site was decreased by guanosine triphosphate and Na+, but increased by divalent cations, implicating coupling with G protein(s). Low affinity [3H]8-OH-DPAT binding site was decreased by cations, especially by monovalent cations and Ca2+. After the destruction of 5-HT neuron by parachloroamphetamine, only the low affinity binding site decreased. These results indicate that [3H]8-OH-DPAT not only labels the 5-HT1A receptor high and low affinity states but has presynaptic binding site relating to 5-HT reuptake site.
Yokota
N
N
Department of Neurology and Psychiatry, Hiroshima University School of Medicine, Japan.
Yamawaki
S
S
Hayakawa
H
H
Yoshida
R
R
Sarai
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002412:Cations / Q000494:pharmacology; D002997:Clomipramine / Q000493:pharmacokinetics; D019204:GTP-Binding Proteins; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000493:pharmacokinetics*; D051381:Rats; D011919:Rats, Inbred Strains; D013764:Tetrahydronaphthalenes / Q000493:pharmacokinetics*
D015306:Biogenic Monoamines; D002412:Cations; D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D002997:Clomipramine