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Plasma serotonin_ pulmonary hypertension and bronchial asthma


									                                                                                     Clinical Science (2002) 103, 345–346 (Printed in Great Britain)   345

       C O R R E S P O N D E N C E

              Plasma serotonin, pulmonary hypertension
                                   and bronchial asthma

Fuad LECHIN*, Bertha VAN DER DIJS* and Alex E. LECHIN†
*Instituto de Medicina Experimental, Universidad Central de Venezuela, Apartado 80.983, Caracas 1080-A, Venezuela, and
†Department of Clinical Sciences, University of Houston, 4800 Calhoun, Houston, TX 77204, U.S.A.

We read with great interest the review article by Strange            REFERENCES
et al. [1]. With respect to it, we would like add some
additional information. In 1994 we presented results                  1 Strange, J. W., Wharton, J., Phillips, P. G. and Wilkins,
                                                                        M. R. (2002) Recent insights into the pathogenesis and
dealing with the increasing levels of catecholamines and                therapeutics of pulmonary hypertension. Clin. Sci. 102,
plasma free serotonin (f-5HT) during asthma attacks [2].                253–268
In 1996 we demonstrated that increased levels of f-5HT                2 Lechin, A. E., Varon, J., van der Dijs, B. and Lechin, F.
                                                                        (1994) Plasma neurotransmitters, blood pressure and
in plasma during asthma attacks were associated with                    heart rate during rest and exercise. Am. J. Respir. Crit.
clinical severity and pulmonary function [3]. In 1998 we                Care Med. 149, A482
                                                                      3 Lechin, F., van der Dijs, B., Orozco, B., Lechin, M. E.
published two research papers showing that tianeptine                   and Lechin, A. E. (1996) Increased levels of free serotonin
(a serotonin-uptake-enhancing drug that reduces plasma                  in plasma of symptomatic asthmatic patients. Ann.
f-5HT) provoked a dramatic and sudden decrease of both                  Allergy Asthma Immunol. 77, 245–253
                                                                      4 Lechin, F., van der Dijs, B., Orozco, B., Jara, H., Rada, I.,
clinical rating and f-5HT plasma levels [4,5]. This                     Lechin, M. and Lechin, A. E. (1998) The serotonin
successful therapeutic strategy has been applied not only               uptake-enhancing drug tianeptine suppresses asthmatic
                                                                        symptoms in children : a double-blind, crossover placebo-
to children and adolescents, but also to adults. Up to                  controlled study. J. Clin. Pharmacol. 38, 918–925
the present, we have successfully treated some 16 000                 5 Lechin, F., van der Dijs, B., Orozco, B., Jara, H., Rada, I.,
asthmatic patients. Twenty four of those patients also                  Lechin, M. and Lechin, A. E. (1998) Neuropharmacologic
                                                                        treatment of bronchial asthma with the antidepressant
present with pulmonary hypertension (PH). Absolute                      tianeptine : a double-blind, crossover placebo-controlled
normalization of PH was obtained in 19 of the patients.                 study. Clin. Pharmacol. Ther. 64, 223–232
                                                                      6 Lechin, F. (2001) Asthma, asthma medication and
Some preliminary information dealing with this issue has                autonomic nervous system dysfunction.
been reported [6–9].                                                    Clin. Physiol. 21, 723
                                                                      7 Lechin, F. and van der Dijs, B. (2002) Serotonin and
   Finally the fact that buspirone, a 5HT-1A agonist                    pulmonary vasoconstriction. J. Appl. Physiol. 92,
which increases plasma f-5HT [10], triggers asthma                      1363–1364
attacks and worsens PH patients [11], provides additional             8 Lechin, F., van der Dijs, B. and Lechin, A. E. (2002)
                                                                        Severe asthma and plasma serotonin. Allergy 57, 258–259
support for the etiopathogenic role of f-5HT in both                  9 Lechin, F., van der Dijs, B. and Lechin, M. E. (2002)
bronchial asthma and pulmonary hypertension.                            Neurocircuitry and Neuroautonomic Disorders. Reviews
                                                                        and Therapeutic Strategies. Chapter 12. Basel : Karger AG
                                                                     10 Lechin, F., van der Dijs, B., Jara, H., Orozco, B., Baez, S.,
                                                                        Benaim, M., Lechin, M. and Lechin, A. (1998) Effects of
                                                                        buspirone on plasma neurotransmitters in healthy
                                                                        subjects. J. Neural Transm. 105, 561–573
                                                                     11 Lechin, F. (2000) Central and plasma 5-HT, vagal tone
                                                                        and airways. Trends Pharmacol. Sci. 21, 425

                                                                                            Received 20 May 2002

Key words : bronchial asthma, plasma serotonin, pulmonary hypertension, therapeutics.
Correspondence : Dr F. Lechin (e-mail flechin!

                                                                     # 2002 The Biochemical Society and the Medical Research Society
346   Correspondence

                       Plasma serotonin, pulmonary hypertension
                            and bronchial asthma: author’s reply

      Julian STRANGE
      Section on Clinical Pharmacology, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 ONN, U.K.

      There is much interest in the role of serotonin (5HT).             REFERENCES
      Recent animal data has demonstrated the attenuation of
      hypoxic-induced pulmonary hypertension (PH) by sero-                1   Eddahibi, S., Raffestin, B., Hanoun, N., Hamon, M. and
                                                                              Adnot, S. (2002) Serotonin transporter inhibitors but not
      tonin transporter (5HTT) inhibitors but interestingly                   serotonin receptor antagonists protect against chronic
      not by 5HT B/ D and 5HT A receptor antagonists [1].                     hypoxic pulmonary hypertension in mice. Am. J. Respir.
                   " "            #                                           Crit. Care Med. 165, A748
      Also cultured pulmonary artery smooth-muscle cells
                                                                          2   Eddahibi, S., Humbert, M., Fadel, E. et al. (2002)
      from patients with primary PH have increased expression                 Hyperplasia of pulmonary artery smooth muscle cells is
      of 5HTT compared with normals and this is associated                    causally related to overexpression of the serotonin
                                                                              transporter in primary pulmonary hypertension. Chest
      with the long (L) variant gene polymorphism for the                     121 (Suppl. 3), S97–S98
      5HTT-linked promoter region, suggesting a genetic
      predisposition [2].

      # 2002 The Biochemical Society and the Medical Research Society

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