Identification of 5-hydroxytryptamine1D binding sites in human brain membranes.
High-affinity, specific 3H-5-hydroxytryptamine (5-HT) binding was analyzed in membrane homogenates of human frontal cortex, caudate, and globus pallidus. 5-HT1A and 5-HT1C binding sites were pharmacologically blocked using 100 nM 8-hydroxy-N,N-dipropyl-2-aminotetralin (8-OH-DPAT) and 100 nM mesulergine, respectively. The majority of 5-HT1 sites remained in each of the three brain regions under these conditions. The pattern of nucleotide interactions with these binding sites (GppNHp = GTP = GDP greater than GMP = adenine nucleotides) suggests a possible linkage to a G protein. RU 24969 competition studies confirmed the absence of 5-HT1B binding sites in human cortex, caudate, and globus pallidus. Drug interactions with putative 5-HT1D binding sites in bovine caudate membranes correlated significantly with their affinities for human membrane recognition sites labeled by 3H-5-HT in the presence of 100 nM 8-OH-DPAT + 100 nM mesulergine. We conclude that the majority of 3H-5-HT labeled recognition sites in human cortex, caudate, and globus pallidus represent 5-HT1D binding sites.
Peroutka
S J
SJ
Department of Neurology, Stanford University School of Medicine, California 94305.
Switzer
J A
JA
Hamik
A
A
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000293:Adolescent; D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D002421:Caudate Nucleus / Q000378:metabolism*; D004873:Ergolines / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D005917:Globus Pallidus / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011985:Receptors, Serotonin / Q000378:metabolism*; D013347:Subcellular Fractions; D013764:Tetrahydronaphthalenes / Q000378:metabolism
D004873:Ergolines; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C031649:mesulergine