Iodine-125 labeled 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane: an iodinated radioligand that specifically labels the agonist high-affinity state of 5-HT2 serotonin receptors

Glennon, Richard A.; Seggel, Mark R.; Soine, William H.; Herrick-Davis, Katherine; Lyon, Robert A.; Titeler, Milt

doi:10.1021/jm00396a003

Cited by 101 publications

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“…Our results show that systemic injection of the phenylalkylamine hallucinogen, DOI, which has high binding affinity for both (Glennon et al, 1988;Appel et al, 1990), decreases levels of noradrenaline in hippocampal dialysates of anaesthetized rats. Both ritanserin and spiperone prevented this inhibitory effect of DOI.…”

Section: Discussionsupporting

confidence: 49%

“…Here we have used the brain microdialysis technique to investigate further the nature of the interaction between 5-HT2/5-HTc receptors and noradrenergic neurones. Noradrenaline release in hippocampus, a major efferent projection of the LC (Foote et al, 1983), was measured following systemic administration of the 5-HT2/5-HTc receptor agonists, DOI and DOB (Glennon et al, 1988;Appel et al, 1990), the non-selective 5-HT agonist, quipazine (Hoyer, 1988), and the 5-HT-releasing agent, pchloroamphetamine (Pettibone & Williams, 1984). A preliminary account of these findings was presented to the British Pharmacological Society (Done & Sharp, 1991 (Done et al, 1992;Sharp & Zetterstrom, 1992 At this time, injection of the x2-adrenoceptor agonist, clonidine (1 mg kg-'), decreases hippocampal noradrenaline output to 90% of pre-drug levels, within 40 min (Done et al, 1992;Sharp & Zetterstrom, 1992), suggesting that a significant proportion of noradrenaline in the dialysates is of neuronal origin.…”

Section: Introductionmentioning

confidence: 99%

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Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

Done¹,

Sharp²

1992

British J Pharmacology

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1 Recent electrophysiological studies have shown that 5-HT215-HTlc receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT,c receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis.2 Subcutaneous administration of the 5-HT2/5-HTc receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane (DOI: 0.2 and 0.5 mg kg-'), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long-lasting (>120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB: 1 mg kg-', s.c.). 3 The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HTc receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-', s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HTc receptors, also antagonized the effect of DOI (0.5 mg kg-', s.c.). Sulpiride (50mg kg-', s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-', s.c.).4 Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-', s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-', s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg', s.c.).5 Our data suggest that in vivo, noradrenaline release in hippocampus is inhibited by 5-HT2 receptor activation. This effect is probably associated with a decrease in noradrenergic neuronal activity.

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Section: Discussionsupporting

confidence: 49%

Section: Introductionmentioning

confidence: 99%

Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

Done¹,

Sharp²

1992

British J Pharmacology

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“…2A) and shortened the latency (data not shown) in mice. DOI, a prototypic phenylalkylamine hallucinogen, has high affinity for 5-HT 2 receptors and is considered to be a useful tool for investigating 5-HT2-mediated responses (8). Consistent with our previous study in rats (9), DOI produced long-lasting and significant increases in the amplitudes of the MSR in mice (Fig.…”

supporting

confidence: 88%

Method for Recording Spinal Reflexes in Mice: Effects of Thyrotropin-Releasing Hormone, DOI, Tolperisone and Baclofen on Monosynaptic Spinal Reflex Potentials

Okada

Honda

Ono

2001

Japanese Journal of Pharmacology

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ABSTRACT-Mice were used to record the spinal reflex potentials and to examine the effects of some drugs upon them. In anesthetized mice, laminectomy was performed in the lumbo-sacral region, and monosynaptic reflex potential (MSR) and polysynaptic reflex potential were recorded from the L5 ventral root after stimulation of the L5 dorsal root. Thyrotropin-releasing hormone (TRH) and 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) produced transient and long-lasting increases in the MSR amplitude, respectively. Tolperisone hydrochloride and baclofen produced transient and long-lasting MSR depressions, respectively. These results show that mice can be used to record spinal reflex potentials, and that it may be possible to study the spinal cord function of mutant and knockout mice using this method. Keywords: Spinal reflex, Monosynaptic reflexSpinal motoneurons are the common final paths to skeletal muscle fibers, and measurement of spinal motor activity is very useful for studying spinal motor functions in the central nervous system. Spinal reflexes are relatively simple to measure, and mono-and polysynaptic reflex potentials have been recorded from the ventral root following stimulation of the dorsal root after laminectomy. In these experiments, relatively large animals such as cats and rats (1), have generally been used due to ease of operation. Recently, mutant and knockout animal models have made an important contribution to the study of various diseases, and these models have usually involved mice. However, there has been no report on mouse spinal reflex experiments due to the difficulty of manipulating such a small animal. In the present study, the conventional method of recording spinal reflex potentials was applied to mouse preparations, and the effects of some centrally acting drugs on the potentials were evaluated in comparison with those in rats.All experimental protocols were approved by the Animal Care and Use Committee of Science University of Tokyo and were in accordance with the guidelines of the National Institutes of Health and The Japanese Pharmacological Society. Forty male ddY mice (38 -42 g, 8-week-old) were anesthetized with urethane (1.6 g / kg, i.p.) and =-chloralose (15 mg/kg, i.p.), and cannulae were inserted into the trachea to maintain respiration and into the caudal vein for drug administration. Intact (non-spinalized) mice were used in this study. Mice were artificially ventilated (0.5 ml/ 100 g body wt, 130 strokes /min: model SN-480-7; Shinano, Tokyo). The dorsal skin was incised along the median line, and the bilateral muscle over the vertebrae was excised to provide a view of the vertebral column. Projections and muscle in the lumbo-sacral region were eliminated with bone forceps (No. 16000-14; FST, Heidelberg, Germany). Very careful laminectomy was performed from the sixth lumbar vertebrae (L6) to L2 with small bone forceps (No. 16015-17, FST). The thin and transparent dura mater of the spinal cord was incised, and both the dorsal and ventral roots below L4 were...

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“…However, the observed K1 for 5-HT at 5-HT2A sites is considerably lower if an agonist radioligand, such as l25J. I -( 2,S-dimethoxy-4-iodophenyl ) -2-aminopropane ([' 251J DOl), is used to label high-affinity "coupled" sites (Titeler et al, 1987;Glennon et al, 1988). The EC 50 of 5-HT for stimulating PLC activity through 5-HT2A receptors was observed to be~300 nM in frontal cortex.…”

Section: Discussionmentioning

confidence: 99%

The Serotonin 5‐HT_2C Receptor Is a Prominent Serotonin Receptor in Basal Ganglia: Evidence from Functional Studies on Serotonin‐Mediated Phosphoinositide Hydrolysis

Wolf

Schutz

1997

Journal of Neurochemistry

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Serotonin (5-hydroxytryptamine; 5-HT) and 5-HT2receptors belong to the class of phosphoinositide-specific phospholipase C (PLC)-linked receptors. Conditions were established for measuring 5-HT2A-linked and 5-HT2~-linkedPLC activity in membranes prepared from previously frozen rat frontal cortex and caudate. In the presence of Ca 2~(300 nM) and GTPyS (1 ftM), 5-HT increased PLC activity in caudate membranes. Pharmacological analysis using the selective 5-HT 2A antagonist, spiperone, and the nonselective 5-HT2AI2C antagonist, mianserin, demonstrated that over half of the 5-HT-stimulated PLC activity was due to stimulation of 5-HT2~receptors as opposed to 5-HT2A receptors. Radioligand binding assays with [ 3H]RP62203 and [3H]-mesulergine were used to quantify 5-HT 2A and 5-HT2s ites, respectively, in caudate. From these data, the Bmax for caudate 5-HT2A sites and 5-HT2~sites was 165.4 ii 9.7 fmol/mg of protein and 49.7 ±3.3 fmol/mg of protein, respectively. In contrast to that in caudate, PLC activity in frontal cortex was stimulated by 5-HT in a manner that was inhibited by the 5-HT2A-selective antagonists, spiperone and ketanserin. Taken together, the results indicate that 5-HT2A-and 5-HT2~-linkedPLC activity can be discerned in brain regions possessing both receptor subtypes using membranes prepared from previously frozen tissue. More importantly, significant 5-HT2~-mediated phosphoinositide hydrolysis was observed in caudate, despite the relatively low density of 5-HT2~sites. The significance of these observations with respect to the physiological function of 5-HT2~receptors is discussed. Key Words: Serotonin receptor-Phospholipase C-Phosphoinositide hydrolysis-Brain-Rat.

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Iodine-125 labeled 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane: an iodinated radioligand that specifically labels the agonist high-affinity state of 5-HT2 serotonin receptors

Cited by 101 publications

References 0 publications

Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

Method for Recording Spinal Reflexes in Mice: Effects of Thyrotropin-Releasing Hormone, DOI, Tolperisone and Baclofen on Monosynaptic Spinal Reflex Potentials

The Serotonin 5‐HT_2C Receptor Is a Prominent Serotonin Receptor in Basal Ganglia: Evidence from Functional Studies on Serotonin‐Mediated Phosphoinositide Hydrolysis

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Iodine-125 labeled 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane: an iodinated radioligand that specifically labels the agonist high-affinity state of 5-HT2 serotonin receptors

Cited by 101 publications

References 0 publications

Evidence that 5‐HT2receptor activation decreases noradrenaline release in rat hippocampusin vivo

Evidence that 5‐HT2receptor activation decreases noradrenaline release in rat hippocampusin vivo

Method for Recording Spinal Reflexes in Mice: Effects of Thyrotropin-Releasing Hormone, DOI, Tolperisone and Baclofen on Monosynaptic Spinal Reflex Potentials

The Serotonin 5‐HT2C Receptor Is a Prominent Serotonin Receptor in Basal Ganglia: Evidence from Functional Studies on Serotonin‐Mediated Phosphoinositide Hydrolysis

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Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

Evidence that 5‐HT₂receptor activation decreases noradrenaline release in rat hippocampusin vivo

The Serotonin 5‐HT_2C Receptor Is a Prominent Serotonin Receptor in Basal Ganglia: Evidence from Functional Studies on Serotonin‐Mediated Phosphoinositide Hydrolysis