Stimulation of the α-adrenoceptor triggers the venom production cycle in the venom gland of Bothrops jararaca

Abstract

The noradrenergic innervation of Bothrops jararaca venom gland is thought to be important in the production and secretion of venom. We investigated the characteristics of the α-adrenoceptor in the venom gland and its role in venom production. This receptor had relatively low sensitivity to noradrenaline (pD2=4.77±0.09, N=7) and to phenylephrine (pD 2=3.77±0.06, N=11). The receptor became desensitized just after venom extraction (pD2 to phenylephrine fell to 3.27±0.02, N=6) and the sensitivity remained low for at least 15 days, returning to normal 30 days after venom extraction, by which time the snake was ready for a new cycle of venom production. Incubation of secretory cells with noradrenaline (10-4 mol l-1 for 5 min) reduced α-adrenoceptor sensitivity to the level seen after venom extraction. Blockade of catecholamine production with reserpine abolished the enlargement of the rough endoplasmic reticulum and the activation of the Golgi apparatus that are normally seen after venom extraction, and the venom production was restored by a single subcutaneous (s.c.) injection of phenylephrine (100 mg kg-1) immediately after venom extraction. Our data suggest that stimulation of the α-adrenoceptor during or shortly after biting is essential for the onset of the venom production cycle.