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.
Ferriere
F
F
Laboratoire de Physiologie, Unité d'Immunophysiologie Générale et Comparée Université de Limoges, Faculté des Sciences, France.
Khan
N A
NA
Troutaud
D
D
Deschaux
P
P
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