![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
A Miyake, S Mochizuki, Y Takemoto and S Akuzawa
Molecular Medicine Research Laboratory, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
The 5-hydroxytryptamine3 receptor 5-HT3R has been implicated in gut and cardiac motility and in behavioral disorders. Characteristics of 5- HT3Rs appear to be heterogeneous among species, but human 5-HT3R cDNA has not been identified. We isolated a cDNA encoding 5-HT3R from human hippocampus. The mouse 5-HT3R gene has been reported to generate two alternative splicing isoforms that differ by six amino acids. All of our isolated human clones corresponded to the shorter isoform. Amino acid identities with mouse neuroblastoma N1E-115 and rat brain 5-HT3Rs were 84% for each. Southern blot analysis of human genomic DNA suggested that our cloned transcript encoded a human counterpart for the rodent 5-HT3Rs. This gene was assigned to chromosome 11 using polymerase chain reaction analysis of a human/rodent somatic cell hybrid panel. With the use of Northern blot analysis, 5-HT3R transcripts were identified in human small intestine, colon, and brain regions including hippocampus, amygdala, and striatum. In human heart, 5-HT3R expression was not detectable even with reverse transcriptase- polymerase chain reaction analysis, although it was detectable in mouse heart. Transfection of COS-1 with human 5-HT3R cDNA induced specific binding of the 5-HT3R-selective radioligand [3H]YM060. Human 5-HT3R showed typical characteristics of the 5-HT3R, but its affinity for the 5-HT3R agonist m-chlorophenylbiguanide was much lower than that of rat 5-HT3R. When injected with human 5-HT3R cRNA, the oocytes responded to 5-HT3R agonists with a rapidly developing inward current. The potency of the agonists to induce inward current paralleled that to compete with the radioligand binding, and 2-methyl-5-hydroxytryptamine, a partial agonist for mouse 5-HT3R, was a full agonist for human 5-HT3R. Our data revealed that the 5-HT3R molecule has interspecies differences in both tissue distribution and functional profile.
This article has been cited by other articles:
|
|
 |
|
  K. Krzywkowski, P. A. Davies, P. L. Feinberg-Zadek, H. Brauner-Osborne, and A. A. Jensen High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor PNAS, January 15, 2008; 105(2): 722 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Niesler, J. Walstab, S. Combrink, D. Moller, J. Kapeller, J. Rietdorf, H. Bonisch, M. Gothert, G. Rappold, and M. Bruss Characterization of the Novel Human Serotonin Receptor Subunits 5-HT3C,5-HT3D, and 5-HT3E Mol. Pharmacol., July 1, 2007; 72(1): 8 - 17. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Iidaka, N. Ozaki, A. Matsumoto, J. Nogawa, Y. Kinoshita, T. Suzuki, N. Iwata, Y. Yamamoto, T. Okada, and N. Sadato A Variant C178T in the Regulatory Region of the Serotonin Receptor Gene HTR3A Modulates Neural Activation in the Human Amygdala J. Neurosci., July 6, 2005; 25(27): 6460 - 6466. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Stoilov, R. Daoud, O. Nayler, and S. Stamm Human tra2-beta1 autoregulates its protein concentration by influencing alternative splicing of its pre-mRNA Hum. Mol. Genet., March 1, 2004; 13(5): 509 - 524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Melke, L. Westberg, S. Nilsson, M. Landen, H. Soderstrom, F. Baghaei, R. Rosmond, G. Holm, P. Bjorntorp, L.-G. Nilsson, et al. A Polymorphism in the Serotonin Receptor 3A (HTR3A) Gene and Its Association With Harm Avoidance in Women Arch Gen Psychiatry, October 1, 2003; 60(10): 1017 - 1023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. S. Sessoms-Sikes, M. E. Hamilton, L.-X. Liu, D. M. Lovinger, and T. K. Machu A Mutation in Transmembrane Domain II of the 5-Hydroxytryptamine3A Receptor Stabilizes Channel Opening and Alters Alcohol Modulatory Actions J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 595 - 604. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P.-B. Tremblay, R. Kaiser, O. Sezer, N. Rosler, C. Schelenz, K. Possinger, I. Roots, and J. Brockmoller Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients J. Clin. Oncol., June 1, 2003; 21(11): 2147 - 2155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Morales and S.-D. Wang Differential Composition of 5-Hydroxytryptamine3 Receptors Synthesized in the Rat CNS and Peripheral Nervous System J. Neurosci., August 1, 2002; 22(15): 6732 - 6741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. K. Machu, M. E. Hamilton, T. F. Frye, C. L. Shanklin, M. C. Harris, H. Sun, T. E. Tenner Jr., F. S. Soti, and W. R. Kem Benzylidene Analogs of Anabaseine Display Partial Agonist and Antagonist Properties at the Mouse 5-Hydroxytryptamine3A Receptor J. Pharmacol. Exp. Ther., December 1, 2001; 299(3): 1112 - 1119. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Lobitz, G. Gisselmann, H. Hatt, and C. H. Wetzel A Single Amino-Acid in the TM1 Domain Is an Important Determinant of the Desensitization Kinetics of Recombinant Human and Guinea Pig {alpha}-Homomeric 5-Hydroxytryptamine Type 3 Receptors Mol. Pharmacol., April 1, 2001; 59(4): 844 - 851. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. D. Spier and S. C. R. Lummis The Role of Tryptophan Residues in the 5-Hydroxytryptamine3 Receptor Ligand Binding Domain J. Biol. Chem., February 25, 2000; 275(8): 5620 - 5625. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Alkondon, E. F. R. Pereira, H. M. Eisenberg, and E. X. Albuquerque Nicotinic Receptor Activation in Human Cerebral Cortical Interneurons: a Mechanism for Inhibition and Disinhibition of Neuronal Networks J. Neurosci., January 1, 2000; 20(1): 66 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Dubin, R. Huvar, M. R. D'Andrea, J. Pyati, J. Y. Zhu, K. C. Joy, S. J. Wilson, J. E. Galindo, C. A. Glass, L. Luo, et al. The Pharmacological and Functional Characteristics of the Serotonin 5-HT3A Receptor Are Specifically Modified by a 5-HT3B Receptor Subunit J. Biol. Chem., October 22, 1999; 274(43): 30799 - 30810. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Miyake, S. Mochizuki, H. Yokoi, M. Kohda, and K. Furuichi New Ether-a-go-go K+ Channel Family Members Localized in Human Telencephalon J. Biol. Chem., August 27, 1999; 274(35): 25018 - 25025. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. J. Coultrap, H. Sun, T. E. Tenner Jr., and T. K. Machu Competitive Antagonism of the Mouse 5-Hydroxytryptamine3 Receptor by Bisindolylmaleimide I, a "Selective" Protein Kinase C Inhibitor J. Pharmacol. Exp. Ther., July 1, 1999; 290(1): 76 - 82. [Abstract] [Full Text]
|
|
|
|
|
|
A. G. Hope, D. Belelli, I. D. Mair, J. J. Lambert, and J. A. Peters Molecular Determinants of (+)-Tubocurarine Binding at Recombinant 5-Hydroxytryptamine3A Receptor Subunits Mol. Pharmacol., June 1, 1999; 55(6): 1037 - 1043. [Abstract] [Full Text]
|
|
|
|
|
|
J. A. van Hooft, A. D. Spier, J. L. Yakel, S. C. R. Lummis, and H. P. M. Vijverberg Promiscuous coassembly of serotonin 5-HT3 and nicotinic alpha 4 receptor subunits into Ca2+-permeable ion channels PNAS, September 15, 1998; 95(19): 11456 - 11461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Miyata, H. Ito, and S. Fukudo Involvement of the 5-HT3 receptor in CRH-induced defecation in rats Am J Physiol Gastrointest Liver Physiol, May 1, 1998; 274(5): G827 - G831. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Lankiewicz, N. Lobitz, C. H. R. Wetzel, R. Rupprecht, G. Gisselmann, and H. Hatt Molecular Cloning, Functional Expression, and Pharmacological Characterization of 5-Hydroxytryptamine3 Receptor cDNA and Its Splice Variants from Guinea Pig Mol. Pharmacol., February 1, 1998; 53(2): 202 - 212. [Abstract] [Full Text]
|
|
|
|
|
|
M. Rosenberg, B. Pie, and E. Cooper Developing Neonatal Rat Sympathetic and Sensory Neurons Differ in Their Regulation of 5-HT3 Receptor Expression J. Neurosci., September 1, 1997; 17(17): 6629 - 6638. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
