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. 1995 Jul;115(6):933–936. doi: 10.1111/j.1476-5381.1995.tb15900.x

Labelling with [125I]-SB 207710 of a small 5-HT4 receptor population in piglet right atrium: functional relevance.

A J Kaumann 1, J A Lynham 1, A M Brown 1
PMCID: PMC1909015  PMID: 7582523

Abstract

1. We investigated the affinity of SB 207710 for sinoatrial 5-HT4 receptors and the density of right atrial 5-HT4 receptors with [125I]-SB 207710 in right atria of new-born piglets. 2. SB 207710 (1-100 nM) antagonized the 5-HT-evoked tachycardia surmountably with a pKB of 9.8. 3. [125I]-SB 207710 (5-1500 pM) labelled a small population of saturable binding sites with a pKD of 10.1 and with 5-HT4 receptor characteristics. The density of atrial binding sites with 5-HT4 receptor characteristics was 174 and 22 times lower respectively than those of atrial beta 1- and beta 2-adrenoceptors, labelled with (-)-[125I]-cyanopindolol. 4. We suggest that the small 5-HT4 receptor population may in part explain why the maximal tachycardia caused by 5-HT is smaller than that caused by catecholamines.

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Selected References

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  1. ARUNLAKSHANA O., SCHILD H. O. Some quantitative uses of drug antagonists. Br J Pharmacol Chemother. 1959 Mar;14(1):48–58. doi: 10.1111/j.1476-5381.1959.tb00928.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
  3. Doménech T., Beleta J., Fernández A. G., Gristwood R. W., Cruz Sánchez F., Tolosa E., Palacios J. M. Identification and characterization of serotonin 5-HT4 receptor binding sites in human brain: comparison with other mammalian species. Brain Res Mol Brain Res. 1994 Jan;21(1-2):176–180. doi: 10.1016/0169-328x(94)90392-1. [DOI] [PubMed] [Google Scholar]
  4. Dumuis A., Sebben M., Bockaert J. The gastrointestinal prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn Schmiedebergs Arch Pharmacol. 1989 Oct;340(4):403–410. doi: 10.1007/BF00167041. [DOI] [PubMed] [Google Scholar]
  5. Grossman C. J., Kilpatrick G. J., Bunce K. T. Development of a radioligand binding assay for 5-HT4 receptors in guinea-pig and rat brain. Br J Pharmacol. 1993 Jul;109(3):618–624. doi: 10.1111/j.1476-5381.1993.tb13617.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kaumann A. J. Do human atrial 5-HT4 receptors mediate arrhythmias? Trends Pharmacol Sci. 1994 Dec;15(12):451–455. doi: 10.1016/0165-6147(94)90058-2. [DOI] [PubMed] [Google Scholar]
  7. Kaumann A. J., Gaster L. M., King F. D., Brown A. M. Blockade of human atrial 5-HT4 receptors by SB 207710, a selective and high affinity 5-HT4 receptor antagonist. Naunyn Schmiedebergs Arch Pharmacol. 1994 May;349(5):546–548. doi: 10.1007/BF00169146. [DOI] [PubMed] [Google Scholar]
  8. Kaumann A. J., Lemoine H. Beta 2-adrenoceptor-mediated positive inotropic effect of adrenaline in human ventricular myocardium. Quantitative discrepancies with binding and adenylate cyclase stimulation. Naunyn Schmiedebergs Arch Pharmacol. 1987 Apr;335(4):403–411. doi: 10.1007/BF00165555. [DOI] [PubMed] [Google Scholar]
  9. Kaumann A. J. Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors. Naunyn Schmiedebergs Arch Pharmacol. 1990 Nov;342(5):619–622. doi: 10.1007/BF00169055. [DOI] [PubMed] [Google Scholar]
  10. Kaumann A. J., Sanders L., Brown A. M., Murray K. J., Brown M. J. A 5-HT4-like receptor in human right atrium. Naunyn Schmiedebergs Arch Pharmacol. 1991 Aug;344(2):150–159. doi: 10.1007/BF00167212. [DOI] [PubMed] [Google Scholar]
  11. Medhurst A. D., Kaumann A. J. Characterization of the 5-HT4 receptor mediating tachycardia in piglet isolated right atrium. Br J Pharmacol. 1993 Nov;110(3):1023–1030. doi: 10.1111/j.1476-5381.1993.tb13916.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Villalón C. M., den Boer M. O., Heiligers J. P., Saxena P. R. Further characterization, by use of tryptamine and benzamide derivatives, of the putative 5-HT4 receptor mediating tachycardia in the pig. Br J Pharmacol. 1991 Jan;102(1):107–112. doi: 10.1111/j.1476-5381.1991.tb12140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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