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Zuleika P. Picarelli - One of the best experts on this subject based on the ideXlab platform.
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Angiotensin receptor in the heart of Bothrops jararaca snake.
European Journal of Pharmacology, 2001Co-Authors: M.cristina Breno, Catarina S. Porto, Zuleika P. PicarelliAbstract:Abstract Angiotensin II interacts with specific cell surface angiotensin AT1 and AT2 receptors and, in some vertebrates, with an atypical angiotensin AT receptor. This study was designed to characterize the angiotensin receptor in the heart of Bothrops jararaca snake. A specific and saturable angiotensin II binding site was detected in cardiac membranes and yielded Kd=7.34±1.41 nM and Bmax=72.49±18 fmol/mg protein. Competition-binding studies showed an angiotensin receptor with low affinity to both angiotensin receptor antagonists, losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole) and PD123319 ((s)-1-(4-[dimethylamino]-3-methylphenyl)methyl-5-(diphenylacetyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylate). Studies on the intracellular signaling pathways showed that phospholipase C/inositol phosphate breakdown and adenylylcyclase/cyclic AMP generation were not coupled with this angiotensin receptor. An adenylylcyclase enzyme sensitive to forskolin was detected. The results indicate the presence of an angiotensin receptor in the heart of B. jararaca snake pharmacologically distinct from angiotensin AT1 and AT2 receptors. It seems to belong to a new class of angiotensin receptors, like some other atypical angiotensin AT receptors that have already been described.
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Some functional aspects of the renin-angiotensin system in the snake Bothrops jararaca
Comparative Biochemistry and Physiology Part A: Physiology, 1994Co-Authors: Maria Fatima Magalhães Lazari, M.c Breno, L.c Abreu, Zuleika P. PicarelliAbstract:Abstract Vasopressor and steroidogenic effects of synthetic angiotensin [Asn 1 , Val 5 ] AII and Bothrops jararaca crude renin were compared in anesthetized Bothrops jararaca snakes. While the intravenous infusion of [Asn 1 , Val 5 ] AII (2.0 μg/kg/min) promoted an arterial blood pressure elevation of 18.2 ± 2.7 mmHg but had no detectable steroidogenic effect, Bothrops jararaca crude renin (0.4 ml/kg/min) induced an increase of both, mean arterial blood pressure (12.8 ± 2.0 mmHg) and plasma corticosterone concentration (85.8 ± 20.1 ng/ml). In vitro experiments indicated that the relative potencies of synthetic angiotensins were [Asn1, Val5] AII 1 , Ile 5 ] AII = (Asp 1 , Val 5 ] AII in B. jararaca uterus, but [Asn 1 , Val 5 ] AII > (Asp 1 Ile 5 ] AII in the guinea-pig ileum. The results indicate that the renin-angiotensin system may be important for the control of blood pressure and steroidogenesis in the snake, although some differences in the structural requirements for angiotensin action occur in this animal when compared to mammals.
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Effects of catecholamines on the isolated aorta of the snake Bothrops jararaca.
Comparative biochemistry and physiology. C Comparative pharmacology and toxicology, 1992Co-Authors: N. Yamanouye, L.c. Salomão, Zuleika P. PicarelliAbstract:1. Effects of catecholamines in snakes have been examined using an aorta preparation isolated from Bothrops jararaca. Adrenaline, noradrenaline and isoprenaline produced dose-dependent contractions on this preparation. The relative potency was adrenaline greater than noradrenaline greater than isoprenaline. 2. Phentolamine displaced, to the right, the concentration-response curve of the three catecholamines tested, showing the presence of alpha-adrenoceptors in this preparation. 3. Isoprenaline has never produced a relaxation, even when the aorta was first contracted by BaCl2 and pretreated with phentolamine, indicating that beta-adrenoceptors are absent in this preparation. 4. In this Bothrops jararaca preparation, exclusively neuronal uptake was found, thus demonstrating that its existence was preserved during evolution.
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Hydrolysis of l-cystine-di-β-naphthylamide and neurohypophyseal peptides by the plasma of the snake Bothrops jararaca
Comparative biochemistry and physiology. B Comparative biochemistry, 1992Co-Authors: P.f. Silveira, L.n. Schiripa, Zuleika P. PicarelliAbstract:Abstract 1. 1. Bothrops jararaca plasma or serum hydrolysed l -cystine-di-β-naphthylamide (CNAse activity) at a degree comparable to that of plasma or serum in pregnant women. 2. 2. In adult snakes, activity was less in males. It was not altered in pregnancy but increased after delivery, being higher at pH 6.4 (unspecific enzymes) than at pH 7.9 (true pregnant woman plasma oxytocinase). 3. 3. Its optimum pH was 5.9, different from that of other known enzymes that hydrolyse the same substrate. 4. 4. Bothrops jararaca plasma also hydrolysed vasopressin, oxytocin and vasotocin. 5. 5. These hydrolysing activities were unexpected for an ovoviviparous reptile.
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Circulating vasotocin in the snake Bothrops jararaca
Comparative biochemistry and physiology. Comparative physiology, 1992Co-Authors: P.f. Silveira, L.n. Schiripa, E Carmona, Zuleika P. PicarelliAbstract:1. There is biochemical and pharmacological evidence to suggest the presence of vasotocin in the blood and plasma of the snake Bothrops jararaca (Bj). 2. XE-64 extracts from Bj blood showed antidiuretic and hypotensive activities in rats and a contractile effect on rat isolated uterus, which was totally dialysable and inhibited by thioglycollate. 3. Extracts from Bj whole plasma presented an antidiuretic activity which was only partially dialysable. 4. The plasma extracts also showed oxytocic properties. 5. When EDTA and Sep-Pak C18 extraction were used, a better recovery and characterization of vasotocin by HPLC was obtained. 6. These results indicate the occurrence of free and bound circulating vasotocin in Bj, in an equilibrium dependent of its enzymatic hydrolysis.
Solange M.t. Serrano - One of the best experts on this subject based on the ideXlab platform.
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Proteomic identification of gender molecular markers in Bothrops jararaca venom.
Journal of proteomics, 2016Co-Authors: André Zelanis, Milene C. Menezes, Eduardo S. Kitano, Tarcísio Liberato, Alexandre K. Tashima, Antônio F.m. Pinto, Nicholas E. Sherman, Jay W. Fox, Solange M.t. SerranoAbstract:Abstract Variation in the snake venom proteome is a well-documented phenomenon; however, sex-based variation in the venom proteome/peptidome is poorly understood. Bothrops jararaca shows significant sexual size dimorphism and here we report a comparative proteomic/peptidomic analysis of venoms from male and female specimens and correlate it with the evaluation of important venom features. We demonstrate that adult male and female venoms have distinct profiles of proteolytic activity upon fibrinogen and gelatin. These differences were clearly reflected in their different profiles of SDS-PAGE, two-dimensional electrophoresis and glycosylated proteins. Identification of differential protein bands and spots between male or female venoms revealed gender-specific molecular markers. However, the proteome comparison by in-solution trypsin digestion and label-free quantification analysis showed that the overall profiles of male and female venoms are similar at the polypeptide chain level but show striking variation regarding their attached carbohydrate moieties. The analysis of the peptidomes of male and female venoms revealed different contents of peptides, while the bradykinin potentiating peptides (BPPs) showed rather similar profiles. Furthermore we confirmed the ubiquitous presence of four BPPs that lack the C-terminal Q–I–P–P sequence only in the female venom as gender molecular markers. As a result of these studies we demonstrate that the sexual size dimorphism is associated with differences in the venom proteome/peptidome in B. jararaca species. Moreover, gender-based variations contributed by different glycosylation levels in toxins impact venom complexity. Biological significance Bothrops jararaca is primarily a nocturnal and generalist snake species, however, it exhibits a notable ontogenetic shift in diet and in venom proteome upon neonate to adult transition. As is common in the Bothrops genus, B. jararaca shows significant sexual dimorphism in snout–vent length and weight, with females being larger than males. This sexual size dimorphism suggests the tendency for female specimens to feed on larger prey, and for male specimens to go on a diet similar to that of juveniles. Variation in the snake venom proteome is a ubiquitous phenomenon occurring at all taxonomic levels. At the intraspecific variation level, the individual contribution to the venom proteome is important but effects contributed by age and feeding habits may also affect the proteome phenotype. Whether sex-based factors play a role in venom variation of a species that shows sexual size dimorphism is poorly known. The use of proteomic strategies supported by transcriptomic data allows a more comprehensive assessment of venom proteomes uncovering components that are gender-specific.
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The proteinase-rich proteome of Bothrops jararaca venom
Toxin Reviews, 2014Co-Authors: Solange M.t. Serrano, Ana K. Oliveira, Milene C. Menezes, André ZelanisAbstract:AbstractBy catalyzing limited proteolysis or extensive degradation, proteolytic enzymes determine the fate of most proteins in an organism. In the evolutionary process of snake venoms, genes encoding proteinases were tailored to generate potent toxins to target key physiological proteins and thereby play a critical role in prey capture, immobilization and defense against predators. In Bothrops jararaca, metalloproteinases and serine proteinases are among the most abundant toxins both in newborn and adult venoms. In this review, we examine the proteinase-rich venom proteome of B. jararaca and how the proteinases act in a complex and heterogeneous fashion to exert their deleterious local and systemic effects.
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Interaction of Bothrops jararaca venom metalloproteinases with protein inhibitors
Toxicon : official journal of the International Society on Toxinology, 2014Co-Authors: Amanda F. Asega, Milene C. Menezes, Ana K. Oliveira, Ana G. C. Neves-ferreira, Solange M.t. SerranoAbstract:Snake venom metalloproteinases (SVMPs) play important roles in the local and systemic hemorrhage observed upon envenomation. In a previous study on the structural elements important for the activities of HF3 (highly hemorrhagic, P-III-SVMP), bothropasin (hemorrhagic, P-III-SVMP) and BJ-PI (non-hemorrhagic, P-I-SVMP), from Bothrops jararaca, it was demonstrated that they differ in their proteolysis profile of plasma and extracellular matrix proteins. In this study, we evaluated the ability of proteins DM43 and α2-macroglobulin to interfere with the proteolytic activity of these SVMPs on fibrinogen and collagen VI and with their ability to induce hemorrhage. DM43 inhibited the proteolytic activity of bothropasin and BJ-PI but not that of HF3, and was not cleaved the three proteinases. On the other hand, α2-macroglobulin did not inhibit any of the proteinases and was rather cleaved by them. In agreement with these findings, binding analysis showed interaction of bothropasin and BJ-PI but not HF3 to DM43 while none of the proteinases bound to α2-macroglobulin. Moreover, DM43 promoted partial inhibition of the hemorrhagic activity of bothropasin but not that of HF3. Our results demonstrate that metalloproteinases of B. jararaca venom showing different domain composition, glycosylation level and hemorrhagic potency show variable susceptibilities to protein inhibitors.
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Individual Variability in the Venom Proteome of Juvenile Bothrops jararaca Specimens
Journal of proteome research, 2013Co-Authors: Gabriela S. Dias, André Zelanis, Eduardo S. Kitano, Ana Helena Pagotto, Sávio Stefanini Sant'anna, Marisa Maria Teixeira Da Rocha, Solange M.t. SerranoAbstract:Snake venom proteomes/peptidomes are highly complex and subject to ontogenetic changes. Individual variation in the venom proteome of juvenile snakes is poorly known. We report the proteomic analysis of venoms from 21 juvenile specimens of Bothrops jararaca of different geographical origins and correlate it with the evaluation of important venom features. Individual venoms showed similar caseinolytic activities; however, their amidolytic activities were significantly different. Rather intriguingly, plasma coagulant activity showed remarkable variability among the venoms but not the prothrombin-activating activity. LC–MS analysis showed significant differences between venoms; however, an interesting finding was the ubiquitous presence of the tripeptide ZKW, an endogenous inhibitor of metalloproteinases. Electrophoretic profiles of proteins submitted to reduction showed significant variability in total proteins, glycoproteins, and in the subproteomes of proteinases. Moreover, identification of differential ...
Regina P. Markus - One of the best experts on this subject based on the ideXlab platform.
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Characterization of β-adrenoceptors responsible for venom production in the venom gland of the snake Bothrops jararaca.
Life sciences, 2000Co-Authors: Norma Yamanouye, Sylvia Mendes Carneiro, Carla N. Scrivano, Regina P. MarkusAbstract:Abstract We have shown that the stimulation of β-adrenoceptors is an important step in venom production in the Bothrops jararaca venom gland. In the present study, the pharmacological profile of the β-adrenoceptor present in Bothrops jararaca venom gland was characterized by radioligand binding assay and by the ability of isoprenaline to promote accumulation of cyclic AMP in dispersed secretory cells. In both cases, the venom glands were obtained from non-extracted snakes (quiescent stage) or from snakes which venom was extracted 4 days before sacrifice (venom production stimulated stage). [ 125 I]-iodocyanopindolol ([ 125 I]-ICYP) bound to extracted gland membranes in a concentration-dependent and saturable manner, but with low affinity. Propranolol, β 1 - or β 2 -selective adrenoceptors ligands displaced the [ 125 I]-ICYP binding with low affinity, while selective β 3 -adrenoceptor ligands did not displace the [ 125 I]-ICYP binding. The displacement of [ 125 I]-ICYP by propranolol was similar in non-extracted and extracted glands, showing the presence of β-adrenoceptors in both stages. In dispersed secretory cells of non-extracted glands, isoprenaline (1 μM) increased the cyclic AMP production and propranolol (10 μM) was able to block this effect. On the other hand, in extracted glands, isoprenaline had no effect. The results suggest that the β-adrenoceptors present in the Bothrops jararaca venom glands are different from those (β 1 , β 2 or β 3 ) described in mammals, but are coupled to the Gs protein, like the known β-adrenoceptor subtypes. Moreover, previous in vivo stimulation of venom production desensitizes the β-adrenoceptors system and, although the receptors could be detected by binding studies, they are not coupled to the Gs protein, indicating that β-adrenoceptors stimulation contributes to the initial steps of venom synthesis.
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Control of venom production and secretion by sympathetic outflow in the snake Bothrops jararaca.
The Journal of experimental biology, 1997Co-Authors: N. Yamanouye, Sylvia Mendes Carneiro, L R Britto, Regina P. MarkusAbstract:Many studies have examined the morphological and biochemical changes in the secretory epithelium of snake venom glands after a bite or milking. However, the mechanisms of venom production and secretion are not yet well understood. The present study was undertaken to evaluate the role of the sympathetic nervous system in the control of venom production and secretion. Venom glands were obtained from Bothrops jararaca (Viperidae) snakes, either unmilked previously or milked 4, 7 or 15 days before they were killed. Levels of tyrosine-hydroxylase-like immunoreactivity were higher in venom glands collected 4 days after milking, coinciding with the maximal synthetic activity of the secretory cells. The only catecholamine detected by high-performance liquid chromatography was noradrenaline, indicating the presence of noradrenergic fibres in these glands. In reserpine-treated milked snakes, no venom could be collected, and electron microscopic analysis showed narrow rough endoplasmic reticulum cisternae, instead of wide cisternae, and less well-developed Golgi apparatus compared with milked untreated snakes, indicating impairment of protein synthesis and secretion. The administration of isoprenaline or phenylephrine (beta- and alpha-adrenoceptor agonists, respectively) to reserpine-treated milked snakes promoted the widening of the rough endoplasmic reticulum and restored venom production, but only phenylephrine restored the development of the Golgi apparatus and the formation of many secretory vesicles. These results provide the first evidence that the sympathetic nervous system plays an important role in venom production and secretion in the venom glands of Bothrops jararaca. Understanding the importance of noradrenergic stimulation in venom production may provide new insights for research into the treatment of snakebites.
Norma Yamanouye - One of the best experts on this subject based on the ideXlab platform.
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The Primary Duct of Bothrops jararaca Glandular Apparatus Secretes Toxins.
Toxins, 2018Co-Authors: Richard H. Valente, Sylvia Mendes Carneiro, Jonas Perales, Fernanda Sakai, José Antonio Portes-junior, Luciana Godoy Viana, Norma YamanouyeAbstract:Despite numerous studies concerning morphology and venom production and secretion in the main venom gland (and some data on the accessory gland) of the venom glandular apparatus of Viperidae snakes, the primary duct has been overlooked. We characterized the primary duct of the Bothrops jararaca snake by morphological analysis, immunohistochemistry and proteomics. The duct has a pseudostratified epithelium with secretory columnar cells with vesicles of various electrondensities, as well as mitochondria-rich, dark, basal, and horizontal cells. Morphological analysis, at different periods after venom extraction, showed that the primary duct has a long cycle of synthesis and secretion, as do the main venom and accessory glands; however, the duct has a mixed mode venom storage, both in the lumen and in secretory vesicles. Mouse anti-B. jararaca venom serum strongly stained the primary duct’s epithelium. Subsequent proteomic analysis revealed the synthesis of venom toxins—mainly C-type lectin/C-type lectin-like proteins. We propose that the primary duct’s toxin synthesis products complement the final venom bolus. Finally, we hypothesize that the primary duct and the accessory gland (components of the venom glandular apparatus) are part of the evolutionary path from a salivary gland towards the main venom gland.
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Characterization of β-adrenoceptors responsible for venom production in the venom gland of the snake Bothrops jararaca.
Life sciences, 2000Co-Authors: Norma Yamanouye, Sylvia Mendes Carneiro, Carla N. Scrivano, Regina P. MarkusAbstract:Abstract We have shown that the stimulation of β-adrenoceptors is an important step in venom production in the Bothrops jararaca venom gland. In the present study, the pharmacological profile of the β-adrenoceptor present in Bothrops jararaca venom gland was characterized by radioligand binding assay and by the ability of isoprenaline to promote accumulation of cyclic AMP in dispersed secretory cells. In both cases, the venom glands were obtained from non-extracted snakes (quiescent stage) or from snakes which venom was extracted 4 days before sacrifice (venom production stimulated stage). [ 125 I]-iodocyanopindolol ([ 125 I]-ICYP) bound to extracted gland membranes in a concentration-dependent and saturable manner, but with low affinity. Propranolol, β 1 - or β 2 -selective adrenoceptors ligands displaced the [ 125 I]-ICYP binding with low affinity, while selective β 3 -adrenoceptor ligands did not displace the [ 125 I]-ICYP binding. The displacement of [ 125 I]-ICYP by propranolol was similar in non-extracted and extracted glands, showing the presence of β-adrenoceptors in both stages. In dispersed secretory cells of non-extracted glands, isoprenaline (1 μM) increased the cyclic AMP production and propranolol (10 μM) was able to block this effect. On the other hand, in extracted glands, isoprenaline had no effect. The results suggest that the β-adrenoceptors present in the Bothrops jararaca venom glands are different from those (β 1 , β 2 or β 3 ) described in mammals, but are coupled to the Gs protein, like the known β-adrenoceptor subtypes. Moreover, previous in vivo stimulation of venom production desensitizes the β-adrenoceptors system and, although the receptors could be detected by binding studies, they are not coupled to the Gs protein, indicating that β-adrenoceptors stimulation contributes to the initial steps of venom synthesis.
Sylvia Mendes Carneiro - One of the best experts on this subject based on the ideXlab platform.
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The Primary Duct of Bothrops jararaca Glandular Apparatus Secretes Toxins.
Toxins, 2018Co-Authors: Richard H. Valente, Sylvia Mendes Carneiro, Jonas Perales, Fernanda Sakai, José Antonio Portes-junior, Luciana Godoy Viana, Norma YamanouyeAbstract:Despite numerous studies concerning morphology and venom production and secretion in the main venom gland (and some data on the accessory gland) of the venom glandular apparatus of Viperidae snakes, the primary duct has been overlooked. We characterized the primary duct of the Bothrops jararaca snake by morphological analysis, immunohistochemistry and proteomics. The duct has a pseudostratified epithelium with secretory columnar cells with vesicles of various electrondensities, as well as mitochondria-rich, dark, basal, and horizontal cells. Morphological analysis, at different periods after venom extraction, showed that the primary duct has a long cycle of synthesis and secretion, as do the main venom and accessory glands; however, the duct has a mixed mode venom storage, both in the lumen and in secretory vesicles. Mouse anti-B. jararaca venom serum strongly stained the primary duct’s epithelium. Subsequent proteomic analysis revealed the synthesis of venom toxins—mainly C-type lectin/C-type lectin-like proteins. We propose that the primary duct’s toxin synthesis products complement the final venom bolus. Finally, we hypothesize that the primary duct and the accessory gland (components of the venom glandular apparatus) are part of the evolutionary path from a salivary gland towards the main venom gland.
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Characterization of β-adrenoceptors responsible for venom production in the venom gland of the snake Bothrops jararaca.
Life sciences, 2000Co-Authors: Norma Yamanouye, Sylvia Mendes Carneiro, Carla N. Scrivano, Regina P. MarkusAbstract:Abstract We have shown that the stimulation of β-adrenoceptors is an important step in venom production in the Bothrops jararaca venom gland. In the present study, the pharmacological profile of the β-adrenoceptor present in Bothrops jararaca venom gland was characterized by radioligand binding assay and by the ability of isoprenaline to promote accumulation of cyclic AMP in dispersed secretory cells. In both cases, the venom glands were obtained from non-extracted snakes (quiescent stage) or from snakes which venom was extracted 4 days before sacrifice (venom production stimulated stage). [ 125 I]-iodocyanopindolol ([ 125 I]-ICYP) bound to extracted gland membranes in a concentration-dependent and saturable manner, but with low affinity. Propranolol, β 1 - or β 2 -selective adrenoceptors ligands displaced the [ 125 I]-ICYP binding with low affinity, while selective β 3 -adrenoceptor ligands did not displace the [ 125 I]-ICYP binding. The displacement of [ 125 I]-ICYP by propranolol was similar in non-extracted and extracted glands, showing the presence of β-adrenoceptors in both stages. In dispersed secretory cells of non-extracted glands, isoprenaline (1 μM) increased the cyclic AMP production and propranolol (10 μM) was able to block this effect. On the other hand, in extracted glands, isoprenaline had no effect. The results suggest that the β-adrenoceptors present in the Bothrops jararaca venom glands are different from those (β 1 , β 2 or β 3 ) described in mammals, but are coupled to the Gs protein, like the known β-adrenoceptor subtypes. Moreover, previous in vivo stimulation of venom production desensitizes the β-adrenoceptors system and, although the receptors could be detected by binding studies, they are not coupled to the Gs protein, indicating that β-adrenoceptors stimulation contributes to the initial steps of venom synthesis.
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Control of venom production and secretion by sympathetic outflow in the snake Bothrops jararaca.
The Journal of experimental biology, 1997Co-Authors: N. Yamanouye, Sylvia Mendes Carneiro, L R Britto, Regina P. MarkusAbstract:Many studies have examined the morphological and biochemical changes in the secretory epithelium of snake venom glands after a bite or milking. However, the mechanisms of venom production and secretion are not yet well understood. The present study was undertaken to evaluate the role of the sympathetic nervous system in the control of venom production and secretion. Venom glands were obtained from Bothrops jararaca (Viperidae) snakes, either unmilked previously or milked 4, 7 or 15 days before they were killed. Levels of tyrosine-hydroxylase-like immunoreactivity were higher in venom glands collected 4 days after milking, coinciding with the maximal synthetic activity of the secretory cells. The only catecholamine detected by high-performance liquid chromatography was noradrenaline, indicating the presence of noradrenergic fibres in these glands. In reserpine-treated milked snakes, no venom could be collected, and electron microscopic analysis showed narrow rough endoplasmic reticulum cisternae, instead of wide cisternae, and less well-developed Golgi apparatus compared with milked untreated snakes, indicating impairment of protein synthesis and secretion. The administration of isoprenaline or phenylephrine (beta- and alpha-adrenoceptor agonists, respectively) to reserpine-treated milked snakes promoted the widening of the rough endoplasmic reticulum and restored venom production, but only phenylephrine restored the development of the Golgi apparatus and the formation of many secretory vesicles. These results provide the first evidence that the sympathetic nervous system plays an important role in venom production and secretion in the venom glands of Bothrops jararaca. Understanding the importance of noradrenergic stimulation in venom production may provide new insights for research into the treatment of snakebites.