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      Role of Vasoactive Intestinal Peptide and 5-HT 2 Receptor Subtype in Serotonin Stimulation of Basal and Thyrotropin-Releasing-Hormone- Induced Prolactin Release in vitro from Rat Pituitary Cells

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          Abstract

          We have previously demonstrated that 5-HT stimulates not only basal but also thyrotropin-releasing-hormone (TRH)-induced prolactin (PRL) release by acting directly at the pituitary gland level. In the present report, the participation of an autoparacrine action of VIP in the stimulatory effects of 5-HT and the involvement of the 5-HT<sub>2</sub> receptor type in mediating serotonin-induced PRL release have been examined. Cultured anterior pituitary cells from ovariectomized adult rats were incubated for 1 h in 1 ml of T<sub>3</sub>-supplemented medium with or without the test substances. The results obtained in the presence of T<sub>3</sub> confirm our previous observations, since treatment of the cells with 5-HT caused dose-dependent increases in basal PRL release, with an approximate EC<sub>50</sub> of 3.68 × 10<sup>–8</sup>  M, and led to a significant potentiation (1.3-fold) of the TRH-induced PRL release. In order to evaluate the possible participation of vasoactive intestinal peptide (VIP) as mediator of the effects of 5-HT on PRL release, cells were incubated in the presence of 5-HT alone (3–1,000 n M) or 100 n M 5-HT plus 30 n M TRH, with or without 200 n M VIP antagonist (VIP-At): [D,4-Cl-Ph<sup>6</sup>,Leu<sup>17</sup>]VIP. VIP-At partially inhibited the release of PRL induced by 5-HT, both basal and TRHstimulated release. The stimulatory effect of 5-HT, however, was not eliminated by VIP-At, since the PRL released in response to 5-HT was still over the respective control ones. These results further support the findings suggesting that 5-HT acts directly at pituitary level by stimulating PRL release. Addition of the 5-HT<sub>2</sub> receptor antagonist, ketanserin (1 µ M) into the incubation medium resulted in the loss of cellular responsiveness to 5-HT, preventing not only the stimulatory effect of 5-HT on the basal but also on the TRH-induced PRL release. In conclusion, the results further strengthen the possibility that 5-HT increases the basal PRL release and potentiates the stimulatory effect of TRH by acting directly at the level of the lactotropes. These effects are not simply a consequence of autoparacrine action of VIP. In addition, it was shown that ketanserin completely antagonizes PRL response to 5-HT, indicating the involvement of the 5-HT<sub>2</sub> receptor type in mediating PRL release.

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          Most cited references 5

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          Receptor binding profile of R 41 468, A novel antagonist at 5-HT2 receptors

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            Effects of pirenperone and ketanserin on rat prolactin secretion in vivo and in vitro

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              The immunocytochemical localization of serotonergic neurons in the rat hypothalamus

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                1998
                January 1998
                16 January 1998
                : 67
                : 1
                : 45-50
                Affiliations
                Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina
                Article
                54297 Neuroendocrinology 1998;67:45–50
                10.1159/000054297
                9485168
                © 1998 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 4, References: 25, Pages: 6
                Categories
                Gonadal Steroids, Gonadotropins and Prolactin

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