Alpha1-adrenoceptors trigger the snake venom production cycle in secretory cells by activating phosphatidylinositol 4,5-bisphosphate hydrolysis and ERK signaling pathway.
Loss of venom from the venom gland after biting or manual extraction leads to morphological changes in venom secreting cells and the start of a cycle of production of new venom. We have previously shown that stimulation of both alpha- and beta-adrenoceptors in the secretory cells of the venom gland is essential for the onset of the venom production cycle in Bothrops jararaca. We investigated the signaling pathway by which the alpha-adrenoceptor initiates the venom production cycle. Our results show that the alpha(1)-adrenoceptor subtype is present in venom gland of the snake. In quiescent cells, stimulation of alpha(1)-adrenoceptor with phenylephrine increased the total inositol phosphate concentration, and this effect was blocked by the phospholipase C inhibitor U73122. Phenylephrine mobilized Ca(2+) from thapsigargin-sensitive stores and increased protein kinase C activity. In addition, alpha(1)-adrenoceptor stimulation increased the activity of ERK 1/2, partially via protein kinase C. Using RT-PCR approach we obtained a partial sequence of a snake alpha(1)-adrenoceptor (260 bp) with higher identity with alpha(1D) and alpha(1B)-adrenoceptors from different species. These results suggest that alpha(1)-adrenoceptors in the venom secreting cells are probably coupled to a G(q) protein and trigger the venom production cycle by activating the phosphatidylinositol 4,5-bisphosphate and ERK signaling pathway.
Laboratório de Farmacologia, Instituto Butantan, Av. Vital Brazil, 1500, 05503-900, São Paulo, SP, Brazil.
Celine M
CM
Kerchove
Milene S A
MS
Luna
Mariana B
MB
Zablith
Maria F M
MF
Lazari
Soraya S
SS
Smaili
Norma
N
Yamanouye
D000818:Animals; D017837:Bothrops; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D020935:MAP Kinase Signaling System; D008297:Male; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000737:chemistry*; D011493:Protein Kinase C / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D012910:Snake Venoms; D019284:Thapsigargin / Q000494:pharmacology
D004791:Enzyme Inhibitors; D004963:Estrenes; D019269:Phosphatidylinositol 4,5-Diphosphate; D011760:Pyrrolidinones; D018340:Receptors, Adrenergic, alpha-1; D012910:Snake Venoms; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019284:Thapsigargin; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium