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Erschienen in: Journal of Gastroenterology 4/2010

01.04.2010 | Original Article—Alimentary Tract

Serotonin transporter activity and serotonin concentration in platelets of patients with irritable bowel syndrome: effect of gender

verfasst von: Leonora Franke, Marco Schmidtmann, Anne Riedl, Ivo van der Voort, Ralf Uebelhack, Hubert Mönnikes

Erschienen in: Journal of Gastroenterology | Ausgabe 4/2010

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Abstract

Background

In the past decade, a strong argument has been built for the role of serotonin (5HT) and the serotonin transporter (SERT) in irritable bowel syndrome (IBS). However, it is still not clear how SERT contributes to this clinically heterogeneous disease. The present study addressed this issue by implementing platelet (plt) markers of SERT activity in the assessment protocol.

Methods

Fasting blood samples of 149 (51 male/98 female) subjects with Rome II and III defined IBS subtypes, and 163 healthy control subjects (CSs; 75 male/88 female) were analyzed for platelet 5HT concentration and 5HT uptake activity [maximum uptake rate (V max) and affinity constant (K m)].

Results

Gender had a significant impact on platelet markers of SERT activity. Male IBS patients showed significantly lower median V max and K m values than the male CS (V max 1.706 vs. 2.148 nmol/109 plts × min, P < 0.001; K m 346 vs. 410 nmol, P = 0.008) without any significant reduction in platelet 5HT concentration (362 vs. 394 ng/109 plts). On the other hand, V max values were not different between female IBS patients and female CS (1.642 vs. 1.741 nmol/109 plts × min), but platelet 5HT concentration was significantly lower in females with diarrhea-predominant IBS (363 vs. 435 ng/109 plts, P < 0.05).

Conclusion

Although an absolute extrapolation from platelets to the gastrointestinal tissue does not appear to be justified, our findings demonstrated that the contribution of disturbed SERT activity to IBS is not uniform and is possibly gender-specific. The results suggest that an assessment of SERT function in platelets may help to elucidate the differences between IBS patients in response to drugs affecting the 5HT system.
Literatur
1.
Zurück zum Zitat Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol. 2000;95(10):2698–709.PubMed Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol. 2000;95(10):2698–709.PubMed
2.
Zurück zum Zitat Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141(8):1285–93.CrossRefPubMed Crowell MD. Role of serotonin in the pathophysiology of the irritable bowel syndrome. Br J Pharmacol. 2004;141(8):1285–93.CrossRefPubMed
3.
Zurück zum Zitat Blundell JE, Lawton CL, Halford JC. Serotonin, eating behavior, and fat intake. Obes Res. 1995;3(Suppl 4):471S–6S.PubMed Blundell JE, Lawton CL, Halford JC. Serotonin, eating behavior, and fat intake. Obes Res. 1995;3(Suppl 4):471S–6S.PubMed
4.
Zurück zum Zitat Lucki I. The spectrum of behaviours influenced by serotonin. Biol Psychiatry. 1998;44(3):151–62.CrossRefPubMed Lucki I. The spectrum of behaviours influenced by serotonin. Biol Psychiatry. 1998;44(3):151–62.CrossRefPubMed
5.
Zurück zum Zitat Bengel D, Jöhren O, Andrews AM, Heils A, Mössner R, Sanvitto GL, et al. Cellular localization and expression of the serotonin transporter in mouse brain. Brain Res. 1997;778(2):338–45.CrossRefPubMed Bengel D, Jöhren O, Andrews AM, Heils A, Mössner R, Sanvitto GL, et al. Cellular localization and expression of the serotonin transporter in mouse brain. Brain Res. 1997;778(2):338–45.CrossRefPubMed
6.
Zurück zum Zitat Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 1996;16(7):2352–64.PubMed Wade PR, Chen J, Jaffe B, Kassem IS, Blakely RD, Gershon MD. Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci. 1996;16(7):2352–64.PubMed
7.
Zurück zum Zitat Chen JX, Pan H, Rothman TP, Wade PR, Gershon MD. Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception. Am J Physiol. 1998;275(3 Pt 1):G433–48.PubMed Chen JX, Pan H, Rothman TP, Wade PR, Gershon MD. Guinea pig 5-HT transporter: cloning, expression, distribution, and function in intestinal sensory reception. Am J Physiol. 1998;275(3 Pt 1):G433–48.PubMed
8.
Zurück zum Zitat Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13–25.CrossRefPubMed Torres GE, Gainetdinov RR, Caron MG. Plasma membrane monoamine transporters: structure, regulation and function. Nat Rev Neurosci. 2003;4(1):13–25.CrossRefPubMed
9.
Zurück zum Zitat Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J Neurosci. 2001;21(16):6348–61.PubMed Chen JJ, Li Z, Pan H, Murphy DL, Tamir H, Koepsell H, et al. Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J Neurosci. 2001;21(16):6348–61.PubMed
10.
Zurück zum Zitat Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126(7):1657–64.CrossRefPubMed Coates MD, Mahoney CR, Linden DR, Sampson JE, Chen J, Blaszyk H, et al. Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology. 2004;126(7):1657–64.CrossRefPubMed
11.
Zurück zum Zitat Camilleri M, Andrews CN, Bharucha AE, Carlson PJ, Ferber I, Stephens D, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132(1):17–25.CrossRefPubMed Camilleri M, Andrews CN, Bharucha AE, Carlson PJ, Ferber I, Stephens D, et al. Alterations in expression of p11 and SERT in mucosal biopsy specimens of patients with irritable bowel syndrome. Gastroenterology. 2007;132(1):17–25.CrossRefPubMed
12.
Zurück zum Zitat Kerckhoffs AP, Ter Linde JJ, Akkermans LM, Samsom M. Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients. Neurogastroenterol Motil. 2008;20(8):900–7.CrossRefPubMed Kerckhoffs AP, Ter Linde JJ, Akkermans LM, Samsom M. Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients. Neurogastroenterol Motil. 2008;20(8):900–7.CrossRefPubMed
13.
Zurück zum Zitat Spiller R, Bennett A. Searching for the answer to irritable bowel syndrome in the colonic mucosa: SERTainty and unSERTainty. Gastroenterology. 2007;132(1):437–41.CrossRefPubMed Spiller R, Bennett A. Searching for the answer to irritable bowel syndrome in the colonic mucosa: SERTainty and unSERTainty. Gastroenterology. 2007;132(1):437–41.CrossRefPubMed
14.
15.
16.
Zurück zum Zitat Franke L, Schewe H-J, Müller B, Campman V, Kitzrow W, Uebelhack R, et al. Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects. Relationship between 5HT content and 5HT uptake. Life Sci. 2000;67:301–15.CrossRefPubMed Franke L, Schewe H-J, Müller B, Campman V, Kitzrow W, Uebelhack R, et al. Serotonergic platelet variables in unmedicated patients suffering from major depression and healthy subjects. Relationship between 5HT content and 5HT uptake. Life Sci. 2000;67:301–15.CrossRefPubMed
17.
Zurück zum Zitat Cicin-Sain L, Froebe A, Bordukalo-Niksic T, Jernej B. Serotonin transporter kinetics in rats selected for extreme values of platelet serotonin level. Life Sci. 2005;77(4):452–61.CrossRefPubMed Cicin-Sain L, Froebe A, Bordukalo-Niksic T, Jernej B. Serotonin transporter kinetics in rats selected for extreme values of platelet serotonin level. Life Sci. 2005;77(4):452–61.CrossRefPubMed
18.
Zurück zum Zitat Franke L, Schewe H-J, Uebelhack R, Müller-Oerlinghausen B. High platelet 5HT uptake activity is associated with a rapid response in depressed patients treated with amitriptyline. Neurosci Lett. 2003;345:105–8.CrossRefPubMed Franke L, Schewe H-J, Uebelhack R, Müller-Oerlinghausen B. High platelet 5HT uptake activity is associated with a rapid response in depressed patients treated with amitriptyline. Neurosci Lett. 2003;345:105–8.CrossRefPubMed
19.
Zurück zum Zitat Franke L, Schewe H-J, Uebelhack R, Berghöfer A, Müller-Oerlinghausen B. Platelet-5HT uptake and gastrointestinal symptoms in patients suffering from major depression. Life Sci. 2003;74:521–31.CrossRefPubMed Franke L, Schewe H-J, Uebelhack R, Berghöfer A, Müller-Oerlinghausen B. Platelet-5HT uptake and gastrointestinal symptoms in patients suffering from major depression. Life Sci. 2003;74:521–31.CrossRefPubMed
20.
Zurück zum Zitat Herwig TA, Farstad M, Vollset SE. Endogeneous serotonin in human blood platelets—factors that may influence reference values. Platelets. 1996;7:47–52.CrossRef Herwig TA, Farstad M, Vollset SE. Endogeneous serotonin in human blood platelets—factors that may influence reference values. Platelets. 1996;7:47–52.CrossRef
21.
Zurück zum Zitat Hrdina PD, Bakish D, Ravindran A, Chudzik J, Cavazzoni P, Lapierre YD. Platelet serotonergic indices in major depression: upregulation of 5-HT2A receptors unchanged by antidepressant treatment. Psychiatry Res. 1997;66:73–85.CrossRefPubMed Hrdina PD, Bakish D, Ravindran A, Chudzik J, Cavazzoni P, Lapierre YD. Platelet serotonergic indices in major depression: upregulation of 5-HT2A receptors unchanged by antidepressant treatment. Psychiatry Res. 1997;66:73–85.CrossRefPubMed
22.
Zurück zum Zitat Mück-Seler D, Jakovljevic M, Pivac N. Platelet 5HT concentrations and suicidal behaviour in recurrent major depression. J Affect Disord. 1996;39:73–80.CrossRefPubMed Mück-Seler D, Jakovljevic M, Pivac N. Platelet 5HT concentrations and suicidal behaviour in recurrent major depression. J Affect Disord. 1996;39:73–80.CrossRefPubMed
23.
Zurück zum Zitat Neuger J, El Khoury A, Kjellman BF, Wahlund B, Aberg-Wistedt A, Stain-Malmgren R. Platelet serotonin functions in untreated major depression. Psychiatry Res. 1999;85(2):189–98.CrossRefPubMed Neuger J, El Khoury A, Kjellman BF, Wahlund B, Aberg-Wistedt A, Stain-Malmgren R. Platelet serotonin functions in untreated major depression. Psychiatry Res. 1999;85(2):189–98.CrossRefPubMed
24.
Zurück zum Zitat Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA. Altered 5-hydroxytryptamine signalling in patients with constipation- and diarrhoea-predominant irritable bowel syndrome. Gastroenterology. 2006;130(1):34–43.CrossRefPubMed Atkinson W, Lockhart S, Whorwell PJ, Keevil B, Houghton LA. Altered 5-hydroxytryptamine signalling in patients with constipation- and diarrhoea-predominant irritable bowel syndrome. Gastroenterology. 2006;130(1):34–43.CrossRefPubMed
25.
Zurück zum Zitat Dunlop SP, Coleman NS, Blackshaw E, Perkins AC, Singh G, Marsden CA, et al. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol. 2005;3(4):349–57.CrossRefPubMed Dunlop SP, Coleman NS, Blackshaw E, Perkins AC, Singh G, Marsden CA, et al. Abnormalities of 5-hydroxytryptamine metabolism in irritable bowel syndrome. Clin Gastroenterol Hepatol. 2005;3(4):349–57.CrossRefPubMed
26.
Zurück zum Zitat Houghton LA, Atkinson W, Whitaker RP, Whorwell PJ, Rimmer MJ. Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome. Gut. 2003;52(5):663–70.CrossRefPubMed Houghton LA, Atkinson W, Whitaker RP, Whorwell PJ, Rimmer MJ. Increased platelet depleted plasma 5-hydroxytryptamine concentration following meal ingestion in symptomatic female subjects with diarrhoea predominant irritable bowel syndrome. Gut. 2003;52(5):663–70.CrossRefPubMed
27.
Zurück zum Zitat Bellini M, Rappelli L, Blandizzi C, Costa F, Stasi C, Colucci R, et al. Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol. 2003;98(12):2705–11.CrossRefPubMed Bellini M, Rappelli L, Blandizzi C, Costa F, Stasi C, Colucci R, et al. Platelet serotonin transporter in patients with diarrhea-predominant irritable bowel syndrome both before and after treatment with alosetron. Am J Gastroenterol. 2003;98(12):2705–11.CrossRefPubMed
28.
Zurück zum Zitat Guicheney P. Human platelet serotonin content: methodological aspects and physiological variations. Methods Find Exp Clin Pharmacol. 1988;10:253–8.PubMed Guicheney P. Human platelet serotonin content: methodological aspects and physiological variations. Methods Find Exp Clin Pharmacol. 1988;10:253–8.PubMed
29.
Zurück zum Zitat Martin F, Rozas G, Miguez J, Aldegunde M. Plasma serotonin: factors affecting its levels. Biog Amines. 1999;7:57–62. Martin F, Rozas G, Miguez J, Aldegunde M. Plasma serotonin: factors affecting its levels. Biog Amines. 1999;7:57–62.
30.
Zurück zum Zitat Payne S. Sex, gender, and irritable bowel syndrome: making the connections. Gend Med. 2004;1(1):18–28.CrossRefPubMed Payne S. Sex, gender, and irritable bowel syndrome: making the connections. Gend Med. 2004;1(1):18–28.CrossRefPubMed
31.
Zurück zum Zitat Heitkemper M, Jarrett M, Bond EF, Chang L. Impact of sex and gender on irritable bowel syndrome. Biol Res Nurs. 2003;5(1):56–65.CrossRefPubMed Heitkemper M, Jarrett M, Bond EF, Chang L. Impact of sex and gender on irritable bowel syndrome. Biol Res Nurs. 2003;5(1):56–65.CrossRefPubMed
32.
Zurück zum Zitat Flachaire E, Beney C, Berthier A, Salandre J, Quincy C, Renaud B. Determination of reference values for serotonin concentration in platelets of healthy newborns, children, adults, and elderly subjects by HPLC with electrochemical detection. Clin Chem. 1990;36:2117–20.PubMed Flachaire E, Beney C, Berthier A, Salandre J, Quincy C, Renaud B. Determination of reference values for serotonin concentration in platelets of healthy newborns, children, adults, and elderly subjects by HPLC with electrochemical detection. Clin Chem. 1990;36:2117–20.PubMed
33.
Zurück zum Zitat Kema IP, Vries EGE, Muskiet FAJ. Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Sci Appl. 2000;747:33–48.CrossRefPubMed Kema IP, Vries EGE, Muskiet FAJ. Clinical chemistry of serotonin and metabolites. J Chromatogr B Biomed Sci Appl. 2000;747:33–48.CrossRefPubMed
34.
Zurück zum Zitat Müller-Oerlinghausen B, Roggenbach J, Franke L. Serotonergic platelet markers of suicidal behaviour—do they really exist? J Affect Disord. 2004;79(1–3):13–24.CrossRefPubMed Müller-Oerlinghausen B, Roggenbach J, Franke L. Serotonergic platelet markers of suicidal behaviour—do they really exist? J Affect Disord. 2004;79(1–3):13–24.CrossRefPubMed
35.
Zurück zum Zitat Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. 1992;33(6):818–24.CrossRefPubMed Heaton KW, Radvan J, Cripps H, Mountford RA, Braddon FE, Hughes AO. Defecation frequency and timing, and stool form in the general population: a prospective study. Gut. 1992;33(6):818–24.CrossRefPubMed
36.
Zurück zum Zitat Hinds JP, Stoney B, Wald A. Does gender or the menstrual cycle affect colonic transit? Am J Gastroenterol. 1989;84(2):123–6.PubMed Hinds JP, Stoney B, Wald A. Does gender or the menstrual cycle affect colonic transit? Am J Gastroenterol. 1989;84(2):123–6.PubMed
37.
Zurück zum Zitat Meier R, Beglinger C, Dederding JP, Meyer-Wyss B, Fumagalli M, Rowedder A, et al. Influence of age, gender, hormonal status and smoking habits on colonic transit time. Neurogastroenterol Motil. 1995;7(4):235–8.PubMed Meier R, Beglinger C, Dederding JP, Meyer-Wyss B, Fumagalli M, Rowedder A, et al. Influence of age, gender, hormonal status and smoking habits on colonic transit time. Neurogastroenterol Motil. 1995;7(4):235–8.PubMed
38.
Zurück zum Zitat Talley NJ, Boyce P, Owen BK. Psychological distress and seasonal symptom changes in irritable bowel syndrome. Am J Gastroenterol. 1995;90(12):2115–9.PubMed Talley NJ, Boyce P, Owen BK. Psychological distress and seasonal symptom changes in irritable bowel syndrome. Am J Gastroenterol. 1995;90(12):2115–9.PubMed
39.
Zurück zum Zitat Douglas WW. Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Gilman AG, Goodman LS, Gilman A, editors. The pharmacological basis of therapeutics. 6th ed. ed. New York: Macmillan; 1980. p. 609–46. Douglas WW. Histamine and 5-hydroxytryptamine (serotonin) and their antagonists. In: Gilman AG, Goodman LS, Gilman A, editors. The pharmacological basis of therapeutics. 6th ed. ed. New York: Macmillan; 1980. p. 609–46.
40.
Zurück zum Zitat Anderson GM, Stevenson JM, Cohen DJ. Steady-state model for plasma free and platelet serotonin in man. Life Sci. 1987;41(15):1777–85.CrossRefPubMed Anderson GM, Stevenson JM, Cohen DJ. Steady-state model for plasma free and platelet serotonin in man. Life Sci. 1987;41(15):1777–85.CrossRefPubMed
41.
Zurück zum Zitat Miwa J, Echizen H, Matsueda K, Umeda N. Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits. Digestion. 2001;63(3):188–94.CrossRefPubMed Miwa J, Echizen H, Matsueda K, Umeda N. Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits. Digestion. 2001;63(3):188–94.CrossRefPubMed
Metadaten
Titel
Serotonin transporter activity and serotonin concentration in platelets of patients with irritable bowel syndrome: effect of gender
verfasst von
Leonora Franke
Marco Schmidtmann
Anne Riedl
Ivo van der Voort
Ralf Uebelhack
Hubert Mönnikes
Publikationsdatum
01.04.2010
Verlag
Springer Japan
Erschienen in
Journal of Gastroenterology / Ausgabe 4/2010
Print ISSN: 0944-1174
Elektronische ISSN: 1435-5922
DOI
https://doi.org/10.1007/s00535-009-0167-y

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