Serotonin Dynamics and Actions in the Rat Carotid Body: Preliminary Findings

  • Maria Ramirez
  • Teresa Gallego-Martin
  • Elena Olea
  • Asuncion Rocher
  • Ana Obeso
  • Constancio GonzalezEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)


Serotonin or 5-HT is a biogenic amine present in the carotid body (CB) of several species as evidenced in many immunocytochemical studies and in a few biochemical measurements. Early literature on 5-HT actions in the CB in all studied species has lead to the conclusion that it does not participate in the setting of conducted action potentials in the sensory nerve of the CB. However, during the last 10 years very important roles in the cellular physiology of the CB have been proposed for this biogenic amine. These roles include a primary role in setting the excitability of chemoreceptor cells via an autocrine or paracrine action, and thereby, the conducted activity in the carotid sinus nerve, and a critical role in the genesis of long term sensory facilitation observed in CBs of animals exposed to intermittent hypoxia. These facts, along with important discrepancies in the endogenous levels of 5-HT in the CB prompted present study conducted in rat CBs. We measured CB endogenous 5-HT content by HPLC with electrochemical detection and found levels of 5-HT in the range of 15–22 pmole/mg tissue in control and chronically hypoxic animals either sustained or intermittent, with no significant differences among them. 5-HT and the 5-HT2A antagonist ketanserin dose-dependently activated chemoreceptor cells as assessed by their capacity to release catecholamines from freshly isolated CB. In preliminary experiments we have observed that intense hypoxia and high extracellular K+ promote a small release of 5-HT from CB which is not dependent on the presence of extracellular Ca2+. Further studies are needed to firmly establish the dynamics of 5-HT in the CB of the rat.


5-HT Carotid body Catecholamine Ketanserin Hypoxia HPLC. 



Supported by Grants BFU2007-61848 (DGICYT), CIBER CB06/06/0050 (ISCiii), and Accion Integrada (Micinn, Spain) PT2009-0172.


  1. Chiocchio SR, Biscardi AM, Tramezzani JH (1967) 5-Hydroxytryptamine in the carotid body of the cat. Science 158(802):790–791PubMedCrossRefGoogle Scholar
  2. Chiocchio SR, King MP, Carballo L, Angelakos ET (1971) Monoamines in the carotid body cells of the cat. J Histochem Cytochem 19(10):621–626PubMedCrossRefGoogle Scholar
  3. Conde SV, Obeso A, Gonzalez C (2007) Low glucose effects on rat carotid body chemoreceptor cells secretory responses and action potential frequency in the carotid sinus nerve. J Physiol 585:721–730PubMedCrossRefGoogle Scholar
  4. Conde SV, Gonzalez C, Batuca JR, Monteiro EC, Obeso A (2008) An antagonistic interaction between A2B adenosine and D2 dopamine receptors modulates the function of rat carotid body chemoreceptor cells. J Neurochem 107(5):1369–1381PubMedCrossRefGoogle Scholar
  5. Dinger B, Gonzalez C, Yoshizaki K, Fidone S (1981) [3 H] spiroperidol binding in normal and denervated carotid bodies. Neurosci Lett 21(1):51–55PubMedCrossRefGoogle Scholar
  6. Fidone S, Gonzalez C, Yoshizaki K (1982) Effects of low oxygen on the release of dopamine from the rabbit carotid body in vitro. J Physiol 333:93–110PubMedGoogle Scholar
  7. Ginzel KH, Kottegoda SR (1954) The action of 5-hydroxytryptamine and tryptamine on aortic and carotid sinus receptors in the cat. J Physiol 123(2):277–288PubMedGoogle Scholar
  8. Gonzalez C, Almaraz L, Obeso A, Rigual R (1992) Oxygen and acid chemoreception in the carotid body chemoreceptors. Trends Neurosci 15(4):146–153PubMedCrossRefGoogle Scholar
  9. Gonzalez C, Almaraz L, Obeso A, Rigual R (1994) Carotid body chemoreceptors: from natural stimuli to sensory discharges. Physiol Rev 74(4):829–898PubMedGoogle Scholar
  10. Gonzalez-Martín MC, Vega-Agapito V, Prieto-Lloret J, Agapito MT, Castañeda J, Gonzalez C (2009) Effects of intermittent hypoxia on blood gases plasma catecholamine and blood pressure. Adv Exp Med Biol 648:319–328PubMedCrossRefGoogle Scholar
  11. Gonzalez-Martín MC, Vega-Agapito MV, Conde SV, Castañeda J, Bustamante R, Olea E, Perez-Vizcaino F, Gonzalez C, Obeso A (2011) Carotid body function and ventilatory responses in intermittent hypoxia evidence for anomalous brainstem integration of arterial chemoreceptor input. J Cell Physiol 226(8):1961–1969PubMedCrossRefGoogle Scholar
  12. Hellström S, Koslow SH (1975) Biogenic amines in carotid body of adult and infant rats–a gas chromatographic-mass spectrometric assay. Acta Physiol Scand 93(4):540–547PubMedCrossRefGoogle Scholar
  13. Hui AS, Striet JB, Gudelsky G, Soukhova GK, Gozal E, Beitner-Johnson D, Guo SZ, Sachleben LR Jr, Haycock JW, Gozal D, Czyzyk-Krzeska MF (2003) Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons. Hypertension 42(6):1130–1136PubMedCrossRefGoogle Scholar
  14. Jacono FJ, Peng YJ, Kumar GK, Prabhakar NR (2005) Modulation of the hypoxic sensory response of the carotid body by 5-hydroxytryptamine: role of the 5-HT2 receptor. Respir Physiol Neurobiol 145(2–3):135–142PubMedCrossRefGoogle Scholar
  15. Kirby GC, McQueen DS (1984) Effects of the antagonists MDL 72222 and ketanserin on responses of cat carotid body chemoreceptors to 5-hydroxytryptamine. Br J Pharmacol 83(1):259–269PubMedCrossRefGoogle Scholar
  16. Mccubbin JW, Green JH, Salmoiraghi GC, Page IH (1956) The chemoceptor stimulant action of serotonin in dogs. J Pharmacol Exp Ther 116(2):191–197PubMedGoogle Scholar
  17. Peng YJ, Overholt JL, Kline D, Kumar GK, Prabhakar NR (2003) Induction of sensory long-term facilitation in the carotid body by intermittent hypoxia: implications for recurrent apneas. Proc Natl Acad Sci U S A 100(17):10073–10078PubMedCrossRefGoogle Scholar
  18. Peng YJ, Yuan G, Jacono FJ, Kumar GK, Prabhakar NR (2006) 5-HT evokes sensory long-term facilitation of rodent carotid body via activation of NADPH oxidase. J Physiol 576(Pt 1):289–295PubMedCrossRefGoogle Scholar
  19. Peng YJ, Nanduri J, Yuan G, Wang N, Deneris E, Pendyala S, Natarajan V, Kumar GK, Prabhakar NR (2009) NADPH oxidase is required for the sensory plasticity of the carotid body by chronic intermittent hypoxia. J Neurosci 29(15):4903–4910PubMedCrossRefGoogle Scholar
  20. Reid G, Rand M (1951) Physiological actions of the partially purified serum vasoconstrictor (serotonin). Aust J Exp Biol Med Sci 29(6):401–415PubMedCrossRefGoogle Scholar
  21. Salmoiraghi GC, Page IH, McCubbin JW (1956) Cardiovascular and respiratory response to intravenous serotonin in rats. J Pharmacol Exp Ther 118(4):477–481PubMedGoogle Scholar
  22. Sapru HN, Krieger AJ (1977) Effect of 5-hydroxytryptamine on the peripheral chemoreceptors in the rat. Res Commun Chem Pathol Pharmacol 16(2):245–250PubMedGoogle Scholar
  23. Schneider JA, Yonkman FF (1954) Species differences in the respiratory and cardiovascular response to serotonin (5-hydroxytryptamine). J Pharmacol Exp Ther 111(1):84–98PubMedGoogle Scholar
  24. Vicario I, Rigual R, Obeso A, Gonzalez C (2000) Characterization of the synthesis and release of catecholamine in the rat carotid body in vitro. Am J Physiol Cell Physiol 278(3):C490–C499PubMedGoogle Scholar
  25. Yoshioka M (1989) Effect of a novel 5-hydroxytryptamine3-antagonist, GR38032F, on the 5-hydroxytryptamine-induced increase in carotid sinus nerve activity in rats. J Pharmacol Exp Ther 250(2):637–641PubMedGoogle Scholar
  26. Zhang M, Nurse CA (2000) Does endogenous 5-HT mediate spontaneous rhythmic activity in chemoreceptor clusters of rat carotid body? Brain Res 872(1–2):199–203PubMedCrossRefGoogle Scholar
  27. Zhang M, Fearon IM, Zhong H, Nurse CA (2003) Presynaptic modulation of rat arterial chemoreceptor function by 5-HT: role of K  +  channel inhibition via protein kinase C. J Physiol 551:825–842PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Maria Ramirez
    • 1
  • Teresa Gallego-Martin
    • 1
  • Elena Olea
    • 1
  • Asuncion Rocher
    • 1
  • Ana Obeso
    • 1
  • Constancio Gonzalez
    • 1
    Email author
  1. 1.Department of Biochemistry and Molecular Biology and Physiology, IBGM School of MedicineUniversity of Valladolid CSIC, CIBERES-Institute Carlos IIIValladolidSpain

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