Skip to main content
SpringerLink
Log in

5-HT3 serotonergic receptor mediation of hypoglycemia-induced arginine-vasopressin but not oxytocin secretion in normal men

  • Published:
Journal of Endocrinological Investigation Aims and scope Submit manuscript

Abstract

The present study was undertaken in order to establish the possible involvement of 5-HT3 serotonergic receptors in the control of basal and/or hypoglycemia-stimulated arginine vasopressin (AVP) and/or oxytocin (OT) secretion. For this purpose, 12 normal men were injected intravenously with a bolus of 4 mg ondansetron, a specific 5-HT3 receptor antagonist, under basal conditions (n= 6) or 30 min before insulin (0.15 lU/kg body weight) administration (n= 6) (insulin tolerance test (ITT)). Control experiments with normal saline instead of ondansetron treatment were performed. Furthermore, on a different occasion, the same subjects were tested in identical experimental conditions with 8 mg ondansetron. Our results showed that the hypoglycemic response to insulin was similar during the ITT and ondansetron plus ITT. Inhibition of 5-HT3 serotonergic receptors with ondansetron (4 or 8 mg) did not modify the basal secretion of AVP and OT and the OT response to insulin-induced hypoglycemia. In contrast, the administration of 4 or 8 mg ondansetron significantly reduced in a similar manner hypoglycemia-induced AVP rise. Mean peak level at 45 min after insulin injection was 2.25 times higher than baseline in the control ITT and 1.5 times higher than basal value in the ondansetron (4 or 8 mg) plus ITT. These data demonstrate that 5-HT3 serotonergic receptors at least partially mediate the AVP response to hypoglycemia, without modifying the simultaneous OT response. On the other hand, 5-HT3 receptors do not appear to be involved in the control of basal posterior pituitary hormone secretions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Van de Kar L. D. Neuroendocrine pharmacology of serotonergic (5-HT) neurons. Ann. Rev. Pharmacol. Toxicol. 31: 289, 1991.

    Article  Google Scholar 

  2. Aravich P.F., Rieg T.S., Ahmed I., Lauterio T.J. Fluoxetine induces vasopressin and oxytocin abnormalities in food-restricted rats given voluntary exercise: relationship to anorexia nervosa. Brain Res. 612: 180, 1993.

    Article  PubMed  CAS  Google Scholar 

  3. Van de Kar L.D., Rittenhouse P.A., Li Q., Levy A.D., Brownfield M.S. Hypothalamic paraventricular, but not supraoptic neurons, mediate the serotonergic stimulation of oxytocin secretion. Brain Res. Bull. 36: 45, 1995.

    Article  PubMed  Google Scholar 

  4. Saydoff J.A., Rittenhouse P.A., Carnes M., Armstrong J., Van de Kar L.D., Brownfield M.S. Neuroendocrine and cardiovascular effects of serotonin: selective role of brain angiotensin on vasopressin. Am. J. Physiol. 270: E513, 1996.

    PubMed  CAS  Google Scholar 

  5. Chiodera P., Volpi R., Capretti L., Caffarri G., Magotti M.G., Coiro V. Different effects of the serotonergic agonists buspirone and sumatriptan on the posterior pituitary hormonal responses to hypoglycemia in humans. Neuropeptides 30: 187, 1996.

    Article  PubMed  CAS  Google Scholar 

  6. Faull C.M., Rooke P., Baylis P.H. The effect of a highly specific serotonin agonist on osmoregulated vasopressin secretion in healthy man. Clin. Endocrinol. 35: 423, 1991.

    Article  CAS  Google Scholar 

  7. Humphrey P.P.A., Hartig P., Hoyer D. A proposed new nomenclature for 5-HT receptors. Trends Pharmacol. Sci. 14: 233, 1993.

    Article  PubMed  CAS  Google Scholar 

  8. Sleight A.J., Pierce P.A., Schmidt A.W., Hekmatpanah C.R., Peroutka S.J. The clinical utility of serotonin receptor active agents in neuropsychiatric disease. In: Peroutka S.J. (Ed.) Serotonin receptor subtypes. Basic and Clinical Aspects. Wiley-Liss, New York, 1991, pp. 211.

    Google Scholar 

  9. Saydoff J.A., Rittenhouse P.A., Van de Kar L.D., Brownfield M.S. Enhanced serotonergic transmission stimulates oxytocin secretion in conscious male rats. J. Pharmacol. Exp. Ther. 257: 95, 1991.

    PubMed  CAS  Google Scholar 

  10. Bagdy G., Kalogeras K.T., Szemeredi K. Effect of 5-HT1C and 5-HT2 receptor stimulation on excessive grooming, penile erection and plasma oxytocin concentrations. Eur. J. Pharmacol. 229: 9, 1992.

    Article  PubMed  CAS  Google Scholar 

  11. Bagdy G., Kalogeras K.T. Stimulation of 5-HT1A and 5-HT2/5-HT1C receptors induce oxytocin release in the male rat. Brain Res. 611: 330, 1993.

    Article  PubMed  CAS  Google Scholar 

  12. Li Q., Levy A.D., Cabrera T.M., Brownfield M.S., Battaglia G., Van de Kar L.D. Long-term fluoxetine, but not desipramine, inhibits the ACTH and oxytocin responses to the 5-HT1A agonist, 8-OH-DPAT, in male rats. Brain Res. 630: 148, 1993.

    Article  PubMed  CAS  Google Scholar 

  13. Bagdy G., Makara G.B. Hypothalamic paraventricular nucleus lesions differentially affect serotonin-1A (5-HT1A) and 5-HT2 receptor agonist-induced oxytocin, prolactin and corticosterone responses. Endocrinology 134: 1127, 1994.

    PubMed  CAS  Google Scholar 

  14. Bagdy G., Sved A.F., Murphy D.L., Szemeredi K. Pharmacological characterization of serotonin receptor subtypes involved in vasopressin and plasma subtypes renin activity responses to serotonin agonists. Eur. J. Pharmacol. 210: 285, 1992.

    Article  PubMed  CAS  Google Scholar 

  15. Pergola P.E., Sved A.F., Voogt J.L., Alper R.H. Effect of serotonin on vasopressin release: a comparison to corticosterone, prolactin and renin. Neuroendocrinology 57: 550, 1993.

    Article  PubMed  CAS  Google Scholar 

  16. Thompson C.J., Jones I.R., Walker M., Baylis P.H., Kendall-Taylor P. The effects of the specific serotonin antagonist ICI 169 369 on the pituitary hormone response to insulin-induced hypoglycemia in humans. Clin. Endocrinol. 36: 235, 1992.

    Article  CAS  Google Scholar 

  17. Barreca T., Franceshini R., Cataldi A., Garibaldi A., Cianciosi P., Rolandi E. Sumatriptan does not affect vasopressin secretion in humans. Clin. Neuropharmacol. 16: 555, 1993.

    Article  PubMed  CAS  Google Scholar 

  18. Butler A., Hill J.M., Jordan C.C., Tyers M.B. Pharmacological properties of GR 38 032F, a novel antagonist at 5-HT3 receptors. Br. J. Pharmacol. 94: 397, 1988.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  19. Hoyer D., Clarke D.E., Fozard J.R., Hartig P.R., Martin G.R., Mylecharane E.J., Saxena P.P., Humphrey P.P.A. International Union of Pharmacology classification of receptors for 5-hydroxy-tryptamine (serotonin). Pharmacol. Rev. 46: 158, 1994.

    Google Scholar 

  20. Chiodera P., Louis F., Legros J.J. Simultaneous radioimmunoassay for plasma argininevasopressin and oxytocin using DEAE Sephadex A25 extraction. J. Endocrinol. Invest. 7: 287, 1984.

    Article  PubMed  CAS  Google Scholar 

  21. Coiro V., Passeri M., Davoli C., d’Amato L., Gelmini G., Fagnoni F., Schianchi L., Bentivolglio M., Volpi R., Chiodera P. Oxytocin response to insulin-induced hypoglycemia in obese subjects before and after weight loss. J. Endocrinol. Invest. 11: 125, 1988.

    Article  PubMed  CAS  Google Scholar 

  22. Barreca T., Corsini G., Cataldi A., Garibaldi A., Cianciosi P., Rolandi E., Franceschini R. Effect of the 5-HT3 receptor antagonist ondansetron on plasma AVP secretion: a study in cancer patients. Biomed. Pharmacother. 50: 512, 1996.

    Article  PubMed  CAS  Google Scholar 

  23. Raff H., Skelton M.M., Merrill D.C., Cowley A.W. Jr. Vasopressin responses to corticotropin releasing factor and hyperosmolality in conscious dogs. Am. J. Physiol. 251: R1235, 1986.

    PubMed  CAS  Google Scholar 

  24. Klingbeil C.K., Keil D., Chang D., Reid I.A. Effects of CRF and ANG II on ACTH and vasopressin release in conscious dogs. Am. J. Physiol. 255: E46, 1988.

    PubMed  CAS  Google Scholar 

  25. Nussey S.S., Page S.R., Peterson D.B., Byrne J., Crosby S.R., White A., Ang V.T.Y., Jackson R., Jenkins J.S. Corticotropin releasing hormone (CRH 1–41) stimulates the secretion of adrenocorticotropin, vasopressin and oxytocin but not adrenocorticotropin precursors: evidence from petrosal sinus sampling in man. Clin. Endocrinol. 34: 51, 1991.

    Article  CAS  Google Scholar 

  26. Kalogeras K.T., Nieman L.K., Friedman T.C., Doppman J.L., Cutler G.B. Jr., Chrousos G.P., Wilder R.L., Gold P.W., Yanovski J.A. Inferior petrosal sinus sampling in healthy human subjects reveals a unilateral corticotropin-releasing hormone-induced arginine vasopressin release associated with ispilateral adrenocorticotropin secretion. J. Clin. Invest. 97: 2045, 1996.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  27. Oomura Y., Yoshimatsu H. Neural network of glucose monitoring system. J. Auton. Nerv. Syst. 10: 359, 1984.

    Article  PubMed  CAS  Google Scholar 

  28. Grant P.J., Stokland M.H., Wiles P.G., Davies J.A., Wales J.K. Hormonal control of homeostasis during hypoglycemia in diabetes mellitus. Thromb. Haemost. 57: 341, 1987.

    PubMed  CAS  Google Scholar 

  29. Chiodera P., Volpi R., Capretti L., Speroni G., Marcato A., Rossi G., Coiro V. Hypoglycemia-induced arginine vasopressin and oxytocin release is mediated by glucoreceptors located inside the blood-brain barrier. Neuroendocrinology 55: 655, 1992.

    Article  PubMed  CAS  Google Scholar 

  30. Yasuda, N., Greer M.A., Aizawa T. Corticotropin-releasing factor. Endocr. Rev. 3: 123, 1982.

    Article  PubMed  CAS  Google Scholar 

  31. Whitnall M.H. Regulation of the hypothalamic corticotropin-releasing hormone neurosecretory system. Progress in Neurobiology 40: 573, 1993.

    Article  PubMed  CAS  Google Scholar 

  32. Coiro V., Butturini U., Gnudi A., Delsignore R., Volpi R., Chiodera P. Nicotinic-cholinergic involvement in arginine-vasopressin response to insulin-induced hypoglycemia in normal men. Metabolism 35: 577, 1986.

    Article  PubMed  CAS  Google Scholar 

  33. Chiodera P., Gnudi A., Bianconi L., Camellini L., Rossi G., Muzzetto P., Fagnoni F., Schianchi L., Volpi R., Coiro V. The infusion of somatostatin reduces the arginine vasopressin response to insulin-induced hypoglycemia in man. J. Endocrinol. Invest. 12: 349, 1989.

    Article  PubMed  CAS  Google Scholar 

  34. Chiodera P., Coiro V. Endogenous opioid mediation of somatostatin inhibition of arginine vasopressin release evoked by insulin-induced hypoglycemia in man. J. Neur. Transm. 33: 121, 1991.

    Article  Google Scholar 

  35. Chiodera P., Volpi R., Coiro V. Inhibitory control of nitric oxide on the arginine-vasopressin and oxytocin response to hypoglycemia in normal men. Neuro Report 5: 1822, 1994.

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dipartimento di Medicina Interna, Università di Parma, Parma, Italy

    Riccardo Volpi M.D., P. Chiodera, N. Giuliani, M. G. Magotti & V. Coiro

  2. Divisione di Medicina Interna, Ospedale di Codogno, Codogno, Italy

    L. Capretti

  3. Laboratorio RIA, Ospedale di Guastalla, Guastalla, Italy

    G. Caffarri

Authors
  1. Riccardo Volpi M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Chiodera
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. Giuliani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Capretti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Caffarri
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. G. Magotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. V. Coiro
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Volpi, R., Chiodera, P., Giuliani, N. et al. 5-HT3 serotonergic receptor mediation of hypoglycemia-induced arginine-vasopressin but not oxytocin secretion in normal men. J Endocrinol Invest 21, 7–11 (1998). https://doi.org/10.1007/BF03347279

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03347279

Key-words

Search

Navigation