Abstract
We measured in human atrium the density of 5-HT4 receptors, labelled with [125I]-SB 207710 (1-butyl-4-piperidinyl) methyl 8-amino-7-iodo-1, (4-benzodioxan-5-carboxylate), and compared it with the density of β1- and β2-adrenoceptors, labelled with (−)-[125I]-cyanopindolol. [125I]-SB 207710 (5–1200 pmol/l) labelled a small population of saturable binding sites (B max ≈ 4 fmol/mg protein) with a pKD of 9.7 and with 5-HT4 receptor characteristics, as assessed with competing ligands. The density of atrial binding sites with 5-HT4 receptor characteristics was 10 and 5 times lower, respectively, than the density of β1- and β2-adrenoceptors. We suggest that the small 5-HT4 receptor population may in part explain why the positive inotropic effects of 5-HT are smaller than those of catecholamines mediated through β1- and β2-adrenoceptors.
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References
Bradford M (1976) A rapid and sensitive method for the quatitation of microgram quantities of protein utilizing the principle of protein-dye-binding. Anal Biochem 72:248–254
Brown AM, Young TJ, Patch TL, Cheung CW Kaumann AJ, Gaster L, King FD (1993) [125I]-SB 207710, a potent, selective radioligand for 5-HT4 receptors. Br J Pharmacol 110:10P
Buxton BF, Jones CR, Molenaar P, Summers RJ (1987) Characterization and autoradiographic localization of β-adrenoceptor subtypes in human cardiac tissues. Br J Pharmacol 92:299–310
Domenech T, Beleta J, Fernandez AG, Gristwood RW, Cruz-Sanchez F, Tolosa E, Palacios JM (1993) Identification and characterization of serotonin 5-HT4 receptor binding sites in human brain: comparison with other mammalian species. Mol Brain Res 21:176–180
Dooley DJ, Bittiger H, Reyman NC (1986) CGP 20712A; a useful tool for quantitating β1- and β2-adrenoceptors. Eur J Pharmacol 130:137–140
Dumuis A, Sebben M; Bockaert J (1989) The gastrokinetic prokinetic benzamide derivatives are agonists at the non-classical 5-HT receptor (5-HT4) positively coupled to adenylate cyclase in neurons. Naunyn-Schmiedeberg's Arch Pharmacol 340:403–410
Gerald Ch, Hartig P, Branchek T, Weinshank RL (1994) DNA encoding 5-HT4 serotonin receptors and uses thereof. International patent WO 94/14957
Gerald Ch, Adham N, Kao H-T, Olsen MA, Laz TM, Schechter LE, Bard JA, Vaysse P J-J, Branchek TA, Weinshank RL (1995) The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 14:2806–2815
Grossman CJ, Kilpatrick GK, Bunce KT (1993) Development of a radioligand binding assay for 5-HT4 receptors in guinea-pig and rat brain. Br J Pharmacol 109:618–624
Hall JA, Kaumann AJ, Brown MJ (1990) Selective β1-adrenoceptor blockade enhances positive isotropic responses to endogenous catecholamines mediated through β2-adrenoceptors, in human atrial myocardium. Circ Res 66:1610–1623
Harding SE, del Monte F, Kaumann AJ (1994) Atrial myocytes from patients taking β blockers have increased positive isotropic responses to 5-hydroxytryptamine. Eur Heart J 15 [suppl]:1130
Hoyer D, Engel G, Berthold R (1982) Binding characteristics of (+)-, (±)- and (−)-[125I]-cyanopindolol to guinea-pig left ventricle membranes. Naunyn-Schmiedeberg's Arch Pharmacol 318:319–329
Kaumann AJ, Lemoine H (1987) β2-adrenoceptor — mediated positive isotropic effect of adrenaline in human ventricular myocardium. Quantitative discrepancies with binding and adenylate cyclase stimulation. Naunyn-Schmiedeberg's Arch Pharmacol 335:403–411
Kaumann AJ (1990) Piglet sinoatrial 5-HT receptors resemble human atrial 5-HT4-like receptors. Naunyn-Schmiedeberg's Arch Pharmacol 342:619–622
Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1990) A 5-hydroxytryptamine receptor in human atrium. Br J Pharmacol 100:879–885
Kaumann AJ, Sanders L, Brown AM, Murray KJ, Brown MJ (1991) A 5-HT4-like receptor in human right atrium. Naunyn-Schmiedeberg's Arch Pharmacol 344:150–159
Kaumann AJ, Gaster LM, King FD, Brown AM (1994) Blockade of human atrial 5-HT4 receptors by SB 207710, a selective and high affinity 5-HT4 receptor antagonist. Naunyn-Schmiedeberg's Arch Pharmacol 349:546–548
Kaumann AJ, Lynham JA, Brown AM (1995) Labelling with [125I]-SB 207710 of a small 5-HT4 receptor population in piglet right atrium: functional relevance. Br J Pharmacol 115:933–936
Leatherbarrow RJ (1992) GRAFIT VERSION 3.0. Erithacus Software Ltd (Staines, UK)
Lemoine H, Schönell H, Kaumann AJ (1988) Contribution of β1- and β2-adrenoceptors of human atrium and ventricle to the effects of noradrenaline and adrenaline as assessed with (−)-atenolol. Br J Pharmacol 95:55–66
Parker S, Taylor M, Hamburger S, Vimal M, Kaumann AJ (1995) SB 203186, a potent antagonist of myocardial 5-HT4 receptors in man and pig. Naunyn-Schmiedeberg's Arch Pharmacol 353:28–35
Sanders L, Kaumann AJ (1992) A 5-HT4-like receptor in human left atrium. Naunyn-Schmiedeberg's Arch Pharmacol 345:382–386
Sanders L, Lynham JA, Bond B, delMonte F, Harding SE, Kaumann AJ (1995) Sensitization of human atrial 5-HT4 receptors by chronic β-blocker treatment. Circulation 92:2526–2539
Ullmer Ch, Schmuck K, Kalkman HO, Lübbert H (1995) Expression of serotonin receptor mRNAs in blood vessels. FEBS Lett 370:215–221
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Kaumann, A.J., Lynham, J.A. & Brown, A.M. Comparison of the densities of 5-HT4 receptors, β1- and β2-adrenoceptors in human atrium: functional implications. Naunyn-Schmiedeberg's Arch Pharmacol 353, 592–595 (1996). https://doi.org/10.1007/BF00169181
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DOI: https://doi.org/10.1007/BF00169181