Autroadiographic characterization of sup 125 I-labeled 2,5-dimethoxy-4-iodophenylisopropylamine (DOI): A phenylisopropylamine derivative labeling both 5HT sub 2 and 5HT sub 1c receptors

Conference · Sun Feb 25 23:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5489268

Appel, N M; Mitchell, W M; Garlick, R K; Glennon, R A; Titeler, M; De Souza, E B ^[1]

---

1. NIDA Addict. Res. Center, Baltimore, MD (United States) Dupont NEN, Boston, MA (United States) MCV/VCU, Richmond, VA (United States) Albany Medical College, NY (United States)

The best-characterized 5HT{sub 2} radioligands, such as ({sup 3}H)ketanserin and ({sup 3}H)spiperone, are antagonists that label both high- and low-affinity states of this receptor. Recently, the radiolabeled phenylisopropylamine hallucinogens DOB and DOI, which are agonists at 5HT{sub 2} receptors, have been demonstrated to label selectively the high-affinity state of brain 5HT{sub 2} receptors. In the present study, the authors determined optimum conditions for autoradiographic visualization of ({sup 125}I)DOI binding and characterized its pharmacology and guanine nucleotide sensitivity under those conditions. In slide-mounted tissue sections (rat forebrain; two 10 {mu}m sections/slide), ({plus minus})({sup 125}I)DOI binding was saturable, of high affinity (K{sub D}{approximately}4nM) and displayed a pharmacological profile (R({minus})DOI > spiperone > DOB > ({plus minus})DOI > ketanserin > S(+)DOI > 5HT > DOM) comparable to that seen in homogenate assays. Consistent with coupling of 5HT{sub 2} receptors to a guanine nucleotide regulatory protein, ({sup 125}I)DOI binding was inhibited by guanine nucleotides but not by ATP. In autoradiograms, high densities of ({sup 125}I)DOI binding sites were present in frontal cortex, olfactory tubercle, claustrum, caudate/putamen and mamillary nuclei with lower densities in trigeminal and solitary nuclei. The highest density of ({sup 125}l)DOI binding was observed in choroid plexus; these binding sites displayed a pharmacological profile characteristic of 5HT{sub 1C} receptors. These data suggest that ({sup 125}I)DOI labels both 5HT{sub 2} and 5HT{sub 1C} receptors.

• OSTI ID: 5489268
• Report Number(s): CONF-9004153--
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 4:3; ISSN FAJOE; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
AUTORADIOGRAPHY
AZAARENES
AZOLES
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CENTRAL NERVOUS SYSTEM
DAYS LIVING RADIOISOTOPES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INDOLES
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPES
KINETICS
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANS
PROTEINS
PYRROLES
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SEROTONIN
SYMPATHOLYTICS
SYMPATHOMIMETICS
TRYPTAMINES
VERTEBRATES