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First published online May 1, 2009
Journal of Experimental Biology 212, 1535-1543 (2009)
Published by The Company of Biologists 2009
doi: 10.1242/jeb.030197
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Sympathetic outflow activates the venom gland of the snake Bothrops jararaca by regulating the activation of transcription factors and the synthesis of venom gland proteins

Milene S. A. Luna1, Thiago M. A. Hortencio1, Zulma S. Ferreira2 and Norma Yamanouye1,*

1 Laboratório de Farmacologia, Instituto Butantan, Av. Vital Brazil 1500, 05503-900, São Paulo, Brazil
2 Departamento de Fisiologia, Instituto de Biociências, Universidade de São Paulo, Rua do Matão, travessa 14, 05508-900, São Paulo, Brazil

* Author for correspondence (e-mail: norma{at}butantan.gov.br)

Accepted 12 March 2009

The venom gland of viperid snakes has a central lumen where the venom produced by secretory cells is stored. When the venom is lost from the gland, the secretory cells are activated and new venom is produced. The production of new venom is triggered by the action of noradrenaline on both {alpha}1- and β-adrenoceptors in the venom gland. In this study, we show that venom removal leads to the activation of transcription factors NF{kappa}B and AP-1 in the venom gland. In dispersed secretory cells, noradrenaline activated both NF{kappa}B and AP-1. Activation of NF{kappa}B and AP-1 depended on phospholipase C and protein kinase A. Activation of NF{kappa}B also depended on protein kinase C. Isoprenaline activated both NF{kappa}B and AP-1, and phenylephrine activated NF{kappa}B and later AP-1. We also show that the protein composition of the venom gland changes during the venom production cycle. Striking changes occurred 4 and 7 days after venom removal in female and male snakes, respectively. Reserpine blocks this change, and the administration of {alpha}1- and β-adrenoceptor agonists to reserpine-treated snakes largely restores the protein composition of the venom gland. However, the protein composition of the venom from reserpinized snakes treated with {alpha}1- or β-adrenoceptor agonists appears normal, judging from SDS-PAGE electrophoresis. A sexual dimorphism in activating transcription factors and activating venom gland was observed. Our data suggest that the release of noradrenaline after biting is necessary to activate the venom gland by regulating the activation of transcription factors and consequently regulating the synthesis of proteins in the venom gland for venom production.

Key words: sympathetic innervation, transcription factors, protein synthesis, exocrine gland, snake, Bothrops jararaca


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