Characterization and distribution of putative 5-ht7 receptors in guinea-pig brain.

British journal of pharmacology ·Vol. 115 ·No. 1 ·1995-05-00 ·Pages 107-16

To ZP, Bonhaus DW, Eglen RM, Jakeman LB

Abstract

1. In the presence of (-)-cyanopindolol (1.0 microM) and sumatriptan (1.0 microM), 0.5 nM [3H]-carboxamidotrytamine ([3H]-5-CT) labelled a single population of receptors in guinea-pig cerebral cortex membranes. 2. 5-HT-displaceable binding was rapid, saturable and reversible. A high affinity binding site was characterized both by equilibrium saturation (Kd = 0.76 +/- 0.28 nM; Bmax = 68.1 +/- 26.7 fmol mg-1 protein) and kinetic (Kd = 0.18 +/- 0.05 nM) analysis. The pharmacological profile of this site was similar to the profile obtained in transfected CHO-K1 cells expressing guinea-pig 5-ht7 receptors. 3. Autoradiographic analysis revealed a discrete localization of binding sites in guinea-pig brain, with the highest density of sites in the medial thalamic nuclei and related limbic and cortical regions. Moderate levels of binding were detected in sensory relay nuclei, substantia nigra, hypothalamus, central grey and dorsal raphe nuclei. This distribution corresponded to that observed using in situ hybridization with [35S]-UTP labelled riboprobes complementary to mRNA encoding the guinea-pig 5-ht7 receptor. 4. In conclusion, under appropriate conditions, [3H]-5-CT labelled a single population of saturable binding sites that corresponded to an endogenous 5-ht7 receptor in guinea-pig brain. The distribution of 5-ht7 receptors in thalamocortical and limbic brain regions suggests a role for these receptors in sensory and affective behaviours.

MeSH Terms

Animals Brain/metabolism CHO Cells Cloning, Molecular Cricetinae Guinea Pigs Ligands Male RNA, Messenger/metabolism Radioligand Assay Receptors, Serotonin/genetics,metabolism Recombinant Proteins/metabolism Serotonin/analogs & derivatives,metabolism Serotonin Receptor Agonists/metabolism

Chemicals

Ligands RNA, Messenger Receptors, Serotonin Recombinant Proteins Serotonin Receptor Agonists Serotonin 5-carboxamidotryptamine

Authors & Affiliations

4 authors, click to expand affiliations / ORCID

To Z P

Institute of Pharmacology, Syntex Discovery Research, Palo Alto, CA 94303, USA.

Bonhaus D W

Eglen R M

Jakeman L B

References (32)

32 references, click to expand

5-Hydroxytryptamine-induced relaxation of isolated mammalian smooth muscle.
Eur J Pharmacol. 1983 Dec 9;96(1-2):71-8 PMID: 6662198
Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT.
Nature. 1983 Sep 8-14;305(5930):140-2 PMID: 6225026
Characterization of a novel 3H-5-hydroxytryptamine binding site subtype in bovine brain membranes.
J Neurosci. 1987 Mar;7(3):894-903 PMID: 2951504
Pharmacological characterization of two 5-hydroxytryptamine receptors coupled to adenylate cyclase in guinea pig hippocampal membranes.
Mol Pharmacol. 1987 Apr;31(4):357-67 PMID: 2952874
Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure.
Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413-7 PMID: 2823261
Further characterization of the 5-HT receptor mediating vascular relaxation and elevation of cyclic AMP in porcine isolated vena cava.
Br J Pharmacol. 1989 May;97(1):292-300 PMID: 2541857
5.HT1 receptors in the vertebrate brain. Regional distribution examined by autoradiography.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Nov;340(5):486-94 PMID: 2533325
Thalamoamygdaloid projections in the rat: a test of the amygdala's role in sensory processing.
J Comp Neurol. 1991 Nov 8;313(2):295-325 PMID: 1765584
Distribution and cellular localization of mRNA coding for 5-HT1A receptor in the rat brain: correlation with receptor binding.
J Neurosci. 1992 Feb;12(2):440-53 PMID: 1531498
Serotonin-induced relaxation in canine coronary artery smooth muscle.
J Pharmacol Exp Ther. 1992 Oct;263(1):123-9 PMID: 1403777
5-Hydroxytryptamine receptors.
Pharmacol Rev. 1992 Sep;44(3):401-58 PMID: 1359584
Autoradiographic mapping of 5-HT1 receptors in the guinea-pig brain with particular reference to the 5-HT1D receptor sites.
Naunyn Schmiedebergs Arch Pharmacol. 1993 Mar;347(3):248-56 PMID: 8479545
A novel rat serotonin receptor: primary structure, pharmacology, and expression pattern in distinct brain regions.
DNA Cell Biol. 1993 Jun;12(5):401-9 PMID: 8517926
Developmental expression of binding sites and messenger ribonucleic acid for vascular endothelial growth factor suggests a role for this protein in vasculogenesis and angiogenesis.
Endocrinology. 1993 Aug;133(2):848-59 PMID: 7688292
Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype.
J Biol Chem. 1993 Aug 25;268(24):18200-4 PMID: 8394362
Molecular cloning of a mammalian serotonin receptor that activates adenylate cyclase.
Mol Pharmacol. 1993 Aug;44(2):229-36 PMID: 8394987
Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation.
Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8547-51 PMID: 8397408
A novel adenylyl cyclase-activating serotonin receptor (5-HT7) implicated in the regulation of mammalian circadian rhythms.
Neuron. 1993 Sep;11(3):449-58 PMID: 8398139
[3H]-5-carboxamidotryptamine labels 5-HT1D binding sites in bovine substantia nigra.
Br J Pharmacol. 1993 Aug;109(4):1206-11 PMID: 8401931
Cloning of a novel human serotonin receptor (5-HT7) positively linked to adenylate cyclase.
J Biol Chem. 1993 Nov 5;268(31):23422-6 PMID: 8226867
Quantitative autoradiography of 5-HT1E binding sites in rodent brains: effect of lesion of serotonergic neurones.
Eur J Pharmacol. 1993 Nov 9;249(2):221-30 PMID: 8287904
Binding of typical and atypical antipsychotic agents to 5-hydroxytryptamine-6 and 5-hydroxytryptamine-7 receptors.
J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10 PMID: 7908055
Cloning and expression of a 5-hydroxytryptamine7 receptor positively coupled to adenylyl cyclase.
J Neurochem. 1994 Aug;63(2):456-64 PMID: 7518496
International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).
Pharmacol Rev. 1994 Jun;46(2):157-203 PMID: 7938165
Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature.
Neuropharmacology. 1994 Mar-Apr;33(3-4):261-73 PMID: 7984266
Molecular biology of 5-HT receptors.
Neuropharmacology. 1994 Mar-Apr;33(3-4):275-317 PMID: 7984267
Localization of 5-HT1B, 5-HT1D alpha, 5-HT1E and 5-HT1F receptor messenger RNA in rodent and primate brain.
Neuropharmacology. 1994 Mar-Apr;33(3-4):367-86 PMID: 7984275
5-Hydroxytryptamine receptors with a 5-HT6 receptor-like profile stimulating adenylyl cyclase activity in pig caudate membranes.
Naunyn Schmiedebergs Arch Pharmacol. 1994 Oct;350(4):356-60 PMID: 7845473
Quantitative autoradiography of 5-HT4 receptors in brains of three species using two structurally distinct radioligands, [3H]GR113808 and [3H]BIMU-1.
Neuropharmacology. 1994 Aug;33(8):1027-38 PMID: 7845549
Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction.
Biochem Pharmacol. 1973 Dec 1;22(23):3099-108 PMID: 4202581
Quantitative analysis of drug-receptor interactions: II. Determination of the properties of receptor subtypes.
Life Sci. 1981 Aug 3;29(5):427-43 PMID: 6116137
Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (-)[125I]iodocyanopindolol, [3H]mesulergine and [3H]ketanserin.
Eur J Pharmacol. 1985 Nov 26;118(1-2):13-23 PMID: 2935410

Article Info

Journal

British journal of pharmacology

Abbr.

Br J Pharmacol

ISSN

0007-1188

DOI

10.1111/j.1476-5381.1995.tb16327.x

Published

1995-05-00

Pages

107-16

Language

English

Region

England

NLM ID

7502536

PMCID

PMC1908750

Subset

External Links

PubMed source DOI: 10.1111/j.1476-5381.1995.tb16327.x PMC Full Text View journal details

Analysis Services

Characterization and distribution of putative 5-ht7 receptors in guinea-pig brain.

Contact

WeChat Official Account