Skip to main content
Log in

Relationship between salivary Chromogranin-A and stress induced by simulated monotonous driving

  • Technical Note
  • Published:
Medical & Biological Engineering & Computing Aims and scope Submit manuscript


The purpose of the present study was to evaluate the use of salivary Chromogranin-A (CgA), which is already used in general as a mental stress marker, for studying the stressful situation created by simulated monotonous driving. After informed consent, 25 healthy male and female subjects were studied under constant environment-controlled conditions. We measured the following physiological variables: blood pressure (BP), cardiac output, total peripheral resistance (TPR), normalized pulse volume (NPV) as an index of alpha-adrenergic sympathetic activity to the finger arteriolar vessels, levels of cortisol and CgA during monotonous driving. The induced stress led to the expected decreases in NPV and increases in TPR and BP caused by peripherally related sympathetic acceleration. However, CgA levels were found to fall gradually in accordance with the gradual increase of subjective rating of stress (SRS) and significantly (p < 0.01) decreased over the period of the simulated monotonous driving. Our hypothesis for the gradual decrease of CgA levels during the simulated monotonous driving is as follows. CgA, catestatin and catecholamines are co-released into the extra-cellular environment. Peripheral sympathetic activity was accelerated by stress resulting from the simulated monotonous driving. Upon peripheral vessel constriction, an increase in TPR then increased BP which, in turn, activated catestatin. Consequently, secretion of CgA was blocked by the co-secreted catestatin from chromaffin granules. The results obtained strongly indicate that, although CgA has been reported as a possible marker of stress, CgA levels are not increased in the stressful situation of simulated monotonous driving.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5





Blood pressure


Cardiac output


Total peripheral resistance


Normalized pulse volume


Subjective rating of stress


  1. Blaschko H, Comline RS, Schneider FH, Silver M, Smith AD (1967) Secretion of a chromaffin granule protein, chromogranin, from the adrenal gland after splanchnic stimulation. Nature 215:58–59. doi:10.1038/215058a0

    Article  Google Scholar 

  2. Deboer RW, Karemaker JM, Strackee J (1987) Hemodynamic fluctuations and baroreflex sensitivity in humans: a beat-to-beat model, Am J Physiol 253 (Heart Circ Physiol 22):680–689

    Google Scholar 

  3. Den R, Toda M, Nagasawa S, Kitamura K, Morimoto K (2007) Circadian rhythm of human salivary CgA. Biomed Res 28(1):57–60. doi:10.2220/biomedres.28.57

    Article  Google Scholar 

  4. Fangwen R, Gen W, Jiaur RG, Madhusudan D, Vaingankar SM, Rana BK, Mahata M, Kennedy BP, Rany M, Salem MPH, Stridsberg M, Abel K, Smith DW, Eleazar EE, Schork NJ, Hamilton BA, Ziegler MG, Mahata SK, O’Connor DT (2007) Catecholamine release—inhibitory peptide catestatin (chromogranin A352–372) naturally occurring amino acid variant Gly364Ser causes profound changes in human autonomic activity and alters risk for hypertension. Circulation 115:2271–2281. doi:10.1161/CIRCULATIONAHA.106.628859

    Article  Google Scholar 

  5. Fujimoto S, Nomura M, Niki M, Motoba H, Ieishi K, Mori T, Ikefuji H, Ito S (2007) Evaluation of stress reactions during upper gastrointestinal endoscopy in elderly patients: assessment of mental stress using chromogranin A. J Med Invest 54(1, 2):140–145

    Article  Google Scholar 

  6. Hakkanen H, Summala H (2001) Fatal traffic accidents among trailer truck drivers and accident causes as viewed by other truck drivers. Accid Anal Prev 32:187–196. doi:10.1016/S0001-4575(00)00030-0

    Article  Google Scholar 

  7. Kakizaki T, Oka T, Kurimori S (1992) Changes in mental workload and fatigue during performance of a mental task. Jpn J Ind Health 34:565–573

    Google Scholar 

  8. Kim T, Loh YP (2005) Chromogranin A: a surprising link between granule biogenesis and hypertension. J Clin Invest 115(7):1711–1713. doi:10.1172/JCI25706

    Article  Google Scholar 

  9. Kim T, Tao-Cheng JH, Eiden LE, Loh YP (2001) Chromogranin A, an “on/off” switch controlling dense-core secretory granule biogenesis. Cell 106:499–509. doi:10.1016/S0092-8674(01)00459-7

    Article  Google Scholar 

  10. Kirschbaum C (1964) Salivery cortisol in psychoneuroendocrine research; recent developments and applications. Pshychoneuroendocriology 19:313–333. doi:10.1016/0306-4530(94)90013-2

    Article  Google Scholar 

  11. Kuhm CM (1989) Handbook of research methods in cardiovascular behavioral medicine. Plenum, New York

    Google Scholar 

  12. Mahata SK, O’Connor DT, Mahata M, Yoo SH, Taupenot L, Wu H, Gill BM, Parmer RJ (1997) Novel autocrine feedback control of catecholamine release. A discrete chromogranin A fragment is a noncompetitive nicotinic cholinergic antagonist. J Clin Invest 100:1623–1633. doi:10.1172/JCI119686

    Article  Google Scholar 

  13. Mahata SK, Mahata M, Parmer RJ, O’Connor DT (1999) Desensitization of catecholamine release: the novel catecholamine release-inhibitory peptide catestatin (chromogranin A344–364) acts at the receptor to prevent nicotinic cholinergic tolerance. J Biol Chem 274:2920–2928. doi:10.1074/jbc.274.5.2920

    Article  Google Scholar 

  14. Mahata SK, Mahata M, Wakade AR, O’Connor DT (2000) Primary structure and function of the catecholamine release inhibitory peptide catestatin (chromogranin A(344–364)): identification of amino acid residues crucial for activity. Mol Endocrinol 14:1525–1535. doi:10.1210/me.14.10.1525

    Article  Google Scholar 

  15. Mahata SK, Mahata M, Wen G, Wong WB, Mahapatra NR, Hamilton BA, O’Connor DT (2004) The catecholamine release-inhibitory “catestatin” fragment of chromogranin A: naturally occurring human variants with different potencies for multiple chromaffin cell nicotinic cholinergic responses. Mol Pharmacol 66(5):1180–1191. doi:10.1124/mol.104.002139

    Article  Google Scholar 

  16. Nakae H, Asami O, Yamada Y, Harada T, Matsui N, Kanno T, Yanaihara N (1998) Salivary chromogranin A as an index of psychosomatic stress response. Biomed Res 19:401–406

    Google Scholar 

  17. Nakagawara M, Yamakoshi K (2000) A portable instrument for non-invasive monitoring of beat-by-beat cardiovascular haemodynamic parameters based on the volume-compensation and electrical-admittance method. Med Biol Eng Comput 38:17–25. doi:10.1007/BF02344683

    Article  Google Scholar 

  18. RING C (2000) Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic, cold pressor, and exercise: Effects of alpha-adrenergic blockade. Psychophysiology 37:634–643. doi:10.1017/S0048577200991030

    Article  Google Scholar 

  19. Sawada Y, Tanaka G, Yamakoshi K (2001) Normalized pulse volume (NPV) derived photo-plethysmographically as a more valid measure of the finger vascular tone. Int J Psychophysiol 41:1–10. doi:10.1016/S0167-8760(00)00162-8

    Article  Google Scholar 

  20. Sushi K, O’Connor DT, Manjula M, Yoo SH et al (1997) Novel autocrine feedback control of catecholamine release: a discrete chromogranin A fragment is a noncompetitive nicotinic cho linergic antagonist. J Clin Invest 100(6):1623–1633. doi:10.1172/JCI119686

    Article  Google Scholar 

  21. Takiyyuddin MA, De Nicola L, Gabbai FB, Dinh TQ, Kennedy B, Ziegler MG, Sabban EL, Parmer RJ, O’Connor DT (1993) Catecholamine secretory vesicles. Augmented chromogranins and amines in secondary hypertension. Hypertension 21:674–679

    Google Scholar 

  22. Taylor CV, Taupenot L, Mahata SK, Mahata M, Wu H, Yasothornsrikul S, Toneff T, Caporale C, Jiang Q, Parmer RJ, Hook VYH, O’Connor DT (2000) Formation of the catecholamine release-inhibitory peptide catestatin from chromogranin A. Determination of proteolytic cleavage sites in hormone storage granules. J Biol Chem 275:22905–22915. doi:10.1074/jbc.M001232200

    Article  Google Scholar 

  23. Thiffault P, Bergeron J (2003) Monotony of road environment and driver fatigue: a simulator study. Accid Anal Prev 35:381–391. doi:10.1016/S0001-4575(02)00014-3

    Article  Google Scholar 

  24. Toroyan and Peden (2007) In: T. Toroyan and M. Peden (eds) Youth and Road Safety, World Health Organization Report, Geneva. Accessible at

  25. Tsigelny I, Mahata SK, Taupenot L, Preece NE, Mahata M, Khan I, Parmer RJ, O’Connor DT (1998) Mechanism of action of chromogranin A on catecholamine release: molecular modeling of the catestatin region reveals a b-strand/loop/bstrand structure secured by hydrophobic interactions and predictive of activity. Regul Pept 77:43–53. doi:10.1016/S0167-0115(98)00040-8

    Article  Google Scholar 

  26. Tsujita S, Morimoto K (1999) Secretory IgA in saliva can be a useful stress marker. Environ Health Prev Med 4(1):1–8. doi:10.1007/BF02931243

    Article  Google Scholar 

  27. Von Euler U (1964) Quantification of stress by catecholamine analysis. Clin Pharmacol Ther 5:398–404

    Google Scholar 

  28. Weitzman ED, Fukushima D, Nogeire C, Roffwarg H, Gallagher TF, Hellman L (1971) 24 Hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab 33:14–22

    Article  Google Scholar 

  29. Wu HJ, Rozansky DJ, Parmer RJ, Gill BM, O’Connor DT (1991) Structure and function of the chromogranin A gene. Clues to evolution and tissue-specific expression. J Biol Chem 266:13130–13134

    Google Scholar 

  30. Yamaguchi M, Kanemori T, Kanemaru M, Mizuno Y, Yoshida H (2001) Correlation of stress and salivary amylase activity. Iyodenshi To Seitai Kogaku 39:234–239

    Google Scholar 

  31. Yamakoshi K (2003) Non-invasive cardiovascular haemodynamic measurements. In: Oberg PA, Togawa T, Spelman F (eds) Sensors in medicine and health care (sensors applications), vol 3. Wiley, Weinheim, pp 107–160

    Chapter  Google Scholar 

  32. Yamakoshi K, Nakagawara M, Tanaka T (2000) Current development in beat-by-beat cardiovascular monitoring with non-invasive and ambulatory techniques. In: Singh M, Radhakrishnan S, Ratil KM, Reddy MRS (eds) Medical diagnostic techniques and procedures. Narosa Publishing House, New Delhi, pp 132–141

    Google Scholar 

  33. Yamakoshi T, Yamakoshi K, Tanaka S, Nogawa M, Sawada Y, Rolfe P (2006) Hemodynamic responses during simulated automobile driving in a monotonous situation. In: Proceedings 28th Annual International Conference of the IEEE Engineering in Medicine and Biology, New York, 5129–5132

  34. Yamakoshi T, Rolfe P, Yamakoshi Y, Hirose H (2009) A novel physiological index for driver’s activation state derived from simulated monotonous driving studies. Transp Res C 17(1):69–80

    Article  Google Scholar 

  35. Yerkes RM, Dodson JD (1908) The relation of strength of stimulus to rapidity of habit-formation. J Comp Neurol Psychol 18:459–482. doi:10.1002/cne.920180503

    Article  Google Scholar 

  36. Yoo SH, Albanesi JP (1991) High capacity, low affinity Ca2þ binding of chromogranin A. Relationship between the pH-induced conformational change and Ca2þ binding property. J Biol Chem 266(12):7740–7745

    Google Scholar 

Download references


The authors would like to give their special thanks to Prof. Ken-ichi Yamakoshi, Kanazawa University, for his valuable suggestions and comments, and Mr. Kenta Matsumura, Hokkaido University, for his technical assistance. We would also like to give our sincere thanks to Prof. Peter Rolfe, OBH Ltd., UK, for his helpful comments on this work and for his assistance in preparing the manuscript. Financial support for this work was partially provided by The Knowledge-based Cluster Creation Project (Ishikawa High-Tech Sensing Cluster) and the Ministry of Education, Science, Sports and Culture, Grant-in-Aid for Scientific Research (B), 17300149, 2007.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Takehiro Yamakoshi.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yamakoshi, T., Park, SB., Jang, WC. et al. Relationship between salivary Chromogranin-A and stress induced by simulated monotonous driving. Med Biol Eng Comput 47, 449–456 (2009).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: