Serotonin modulation of lymphocyte proliferation via 5-HT1A receptors in rainbow trout (Oncorhynchus mykiss).
In this study, the effects of serotonin (5-HT) on in vitro lymphoproliferation in rainbow trout (Oncorhynchus mykiss) are investigated. Serotonin exerted immunosuppressive effects on lipopolysaccharide (LPS) and phytohemagglutinin (PHA)-stimulated proliferation of fish peripheral blood lymphocytes (PBL). 8-OH-DPAT (an agonist of 5-HT1A receptors) mimicked the inhibitory effects of serotonin on lymphocyte proliferation, whereas addition of spiperone (an antagonist of 5-HT1A and 5-HT1B receptors) reversed these inhibitory effects, indicating that 5-HT1A receptors may be implicated in serotonin-induced immunosuppression. Furthermore, in this study the serotonergic receptors present on fish peripheral lymphocytes were characterized. A Scatchard plot of serotonin binding to fish lymphocytes followed the 'bell' shape curve with a Bmax of 0.63 microM and a Kd of 1.54 x 10(-8) M/10(6) cells. These results demonstrate the presence of positive-type co-operation among receptor populations. In a displacement study, serotonin inhibited the binding of 3H-5HT to the receptor sites both in resting and LPS/PHA-stimulated trout lymphocytes. Interestingly, the agonists (8-OH-DPAT and buspirone) and antagonist (NAN-190) of the 5-HT1A receptor subtype failed to displace 3H-5HT binding to receptor sites in resting cells, whereas these agents inhibited 3H-5HT binding in LPS- and PHA-stimulated lymphocytes significantly, suggesting that after mitogenic stimulation, 5-HT1A receptors are expressed on lymphocytes. CGS-12066B (an agonist of 5-HT1B receptors) failed to influence significantly 3H-5HT binding to receptor sites both in resting and mitogen-stimulated lymphocytes, indicating that the 5-HT receptor subpopulation is not expressed either on resting or on LPS- or PHA-stimulated lymphocytes. Taken together, these results suggest that trout peripheral blood lymphocytes express functional serotonergic receptors, and 5-HT1A receptors, which are not expressed by resting lymphocytes, are expressed after mitogenic stimulation and implicated in the inhibition of mitogenic (LPS and PHA) responses.
Laboratoire de Physiologie, Unité d'Immunophysiologie Générale et Comparée Université de Limoges, Faculté des Sciences, France.
F
F
Ferriere
N A
NA
Khan
D
D
Troutaud
P
P
Deschaux
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000378:metabolism; D017686:Oncorhynchus mykiss; D011485:Protein Binding / Q000276:immunology; D011985:Receptors, Serotonin / Q000378:metabolism / Q000502:physiology*; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*
D000276:Adjuvants, Immunologic; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin