Sympathetic outflow activates the venom gland of the snakeBothrops jararacaby regulating the activation of transcription factors and the synthesis of venom gland proteins

Abstract

SUMMARYThe 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 bothα 1- and β-adrenoceptors in the venom gland. In this study, we show that venom removal leads to the activation of transcription factors NFκB and AP-1 in the venom gland. In dispersed secretory cells,noradrenaline activated both NFκB and AP-1. Activation of NFκB and AP-1 depended on phospholipase C and protein kinase A. Activation of NFκB also depended on protein kinase C. Isoprenaline activated both NFκB and AP-1, and phenylephrine activated NFκB 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 α1- 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 α1- 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.