4-(2'-Methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p-iodobenzamido]-ethyl- piperazine ([125I]p-MPPI) as a new selective radioligand of serotonin-1A sites in rat brain: in vitro binding and autoradiographic studies.
Binding characteristics of a radioiodinated serotonin-1A (5-HT1A) receptor antagonist, 4-(2'-methoxy-phenyl)-1-[2'-(n-2"-pyridinyl)-p- iodobenzamido]-ethyl-piperazine ([125I]p-MPPI) were evaluated using in vitro homogenate binding and autoradiographic techniques in rat brains. [125I]p-MPPI displayed a Kd value of 0.32 +/- 0.04 nM (in the presence of MgCl2) and a Bmax value of 315 +/- 60 fmol/mg of protein in rat hippocampal homogenates. The number of 5-HT1A receptors labeled by [125I]p-MPPI was 40% higher than that labeled by trans-8-hydroxy-2-(N-n-propyl-N-3'-iodo-2'- propenyl)aminotetralin ([125I]R(+)8-OH-PIPAT) (225 +/- 47 fmol/mg of protein), a radioiodinated 5-HT1A agonist. The magnesium ion showed an inhibitory effect on [125I]p-MPPI binding but increased the specific binding of [125I]R(+)8-OH-PIPAT. A significant increase in Bmax values in the presence of guanyl nucleotides was observed for [125I]p-MPPI (control, 307 +/- 35 fmol/mg of protein; with GTP, 345 +/- 30 fmol/mg of protein; with guanylyl-imidodiphosphate, 362 +/- 35 fmol/mg of protein); however, both guanyl nucleotides significantly reduced the Bmax values measured by [125I]R(+)8-OH-PIPAT (control, 213 +/- 50 fmol/mg of protein; with GTP, 133 +/- 20 fmol/mg of protein; with guanylyl-imidodiphosphate, 108 +/- 20 fmol/mg of protein). The binding characteristics of [125I]p-MPPI for 5-HT1A receptors suggest that p-MPPI is an antagonist for 5-HT1A receptors. In vitro autoradiographic studies in rat brain sections with [125I]p-MPPI showed specific labeling of areas rich in 5-HT1A receptors and the regional distribution closely matched those labeled by [125I]R(+)8-OH-PIPAT.(ABSTRACT TRUNCATED AT 250 WORDS)
Kung
M P
MP
Department of Radiology, University of Pennsylvania, Philadelphia.
Frederick
D
D
Mu
M
M
Zhuang
Z P
ZP
Kung
H F
HF
D000631:Aminopyridines / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D006150:Guanine Nucleotides / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists
D000631:Aminopyridines; D006150:Guanine Nucleotides; D010879:Piperazines; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; C087205:4-(2'-methoxyphenyl)-1-(2'-(N-(2''-pyridinyl)-4-iodobenzamido)ethyl)piperazine; D008274:Magnesium