Acta physiologica, pharmacologica et therapeutica latinoamericana : organo de la Asociacion Latinoamericana de Ciencias Fisiologicas y [de] la Asociacion Latinoamericana de Farmacologia最新文献

The aim of the investigation was to examine the effects of cooling on the tail artery regarding the scarceness of such studies in spite of the essential thermoregulatory role played by this vessel. Segments of the proximal portion were suspended isometrically in medium containing 1.25 mM Ca. Lowering the temperature to 25 degrees C increased the sensitivity and maximum strength of the adrenaline concentration-effect curves. These changes were reversed by warming back to 37 degrees C. Cocaine attenuated the increase of sensitivity without changing the increase of the maximum response. Either the sensitivity and strength of the responses to phenylephrine and serotonin were increased by cooling. Clonidine evoked weak contractions in 18 out of 38 experiments. After cooling, the responses persisted only in 7 arteries and the strength was almost halved. Responses to field electric stimulation at 25 degrees C exhibited a pronounced increase of strength and a small increase of sensitivity. -log Kb for prazosin against adrenaline was increased by cooling (8.7 and 9.1 at 37 degrees C and 25 degrees C, P < 0.01). After partial receptor inactivation using phenoxybenzamine, the dissociation-constant (KA) indicated a moderate affinity for phenylephrine that was not changed by cooling (4.1 and 4.2 x 10(-6) at 37 degrees and 25 degrees C respectively). Receptor reserve and occupancy at EC50 also remained unchanged at 25 degrees C. It can be concluded that: 1) cooling increases the tail artery reactivity, partly as a consequence of the inhibition of adrenergic neuronal uptake; 2) responsiveness to alpha 2-agonists is not involved in the effects of cooling whereas the role of alpha 1-adrenoceptor could not be properly clarified; 3) cooling may facilitate some steps of the contractile activation beyond the agonist-receptor interaction.

A study of hemorrhagic, edema-forming, proteolytic and myonecrotic activities induced by newborn Bothrops alternatus snake venoms from Argentina was performed. The analyzed venom had these activities with markedly differences when compared with the venom of adult specimens. Hemorrhagic activity was four times higher, while edema forming activity was ten times or more. But proteolytic activity was similar in both groups. Hystological analysis showed intense hemorrhage and muscular fiber myolisis after 60 minutes of venom injection. Myonecrosis and inflammatory exudate were higher in the following hours. Hemorrhage decreased after 24 hours and muscular fiber regeneration started after the first week with granulation tissue formation. On the fourth week regenerating muscular fiber areas and granulation tissue were still observed. As a conclusion, we can assume that the injury induced in the snake accident by newborn Bothrops alternatus snakes would be more intense than those induced by the adult ones.

Propinox is an antispasmodic drug frequently used in the treatment of disorders of the gastrointestinal tract, the uterus and the gallbladder, but little is known about its relaxing activity in gallbladder tissue. The main objective of this study was to determine the antispasmodic activity of propinox, compared to other antispasmodics, in the gallbladder and to assess its binding affinity to receptor sites which may be involved in its mechanism of action. Antispasmodic activity of propinox, (-) scopolamine-n-butyl bromide, atropine and verapamil was determined in human gallbladders to reduce the risk of interspecies variability. Inhibitory activities (ED50) of carbachol-induced contraction were: atropine 5.03 x 10(-8) M > propinox 1.25 x 10(-7) M > verapamil 6.63 x 10(-6) M > (-) scopolamine-n-butyl bromide 5.4 x 10(-5) M. pD'2 for propinox was 6.94, indicating non competitive inhibition of carbachol action. Radioligand binding studies were performed to determine if the antispasmodic action of the drug involved binding to muscarinic receptors or calciumantagonist sites. The inhibition constant (Ki) of propinox for muscarinic receptors of guinea pig ileum smooth muscle, which contains a mixed M2-M3 receptor population, was 1.6 x 10(-6) M. Ki for brain muscarinic receptors (M1) was 1.0 x 10(-4) M, for cardiac receptors (M2) 1.2 x 10(-6) M and from salivary gland receptors (M3) 1.5 x 10(-6) M. For binding to the dihidropiridine calcium antagonist binding sites, Ki were: 4.9 x 10(-5) M for propinox and 2.2 x 10(-7) M for verapamil. For the phenylalkylamine binding sites Ki were: 5.0 x 10(-6) M for propinox and 3.5 x 10(-8) M for verapamil. For the benzothiacepine binding sites, Ki for propinox was 5.2 x 10(-6) M. The following may be concluded: 1.--The antispasmodic activity of propinox in isolated human gallbladder was comparatively less potent than that of atropine and more potent than those of verapamil and (-) scopolamine-n-butyl bromide. 2.--Propinox showed binding to muscarinic and calcium receptors that can be related to its antispasmodic activity; suggesting that the drug is an antispasmodic with anticholinergic and musculotropic activity. 3.--The dual mechanism of action, anticholinergic and calcium-blocking, would induce synergism of pharmacodynamic effects and minimize adverse events of pure antimuscarinic drugs or calcium antagonists.

The limbic structures play an important role in the control of the neuroendocrine and sympathical adrenal function in basal and stress conditions. This work was undertaken to evaluate plasma ACTH, adrenocortical activity, cardiac adrenoceptors density and affinity response to variable chronic stress (VCS) in anterodorsal thalamic nuclei (ADTN) lesioned rats. Thirty days after lesion, shamlesioned stressed animals increased plasma ACTH and corticosterone as compared to sham-lesioned unstressed animals (p < 0.05); lesioned rats increased ACTH levels after VCS (p < 0.05) as compared to unstressed-lesioned rats. Whereas in sham-lesion plasma corticosterone (C) increased after stress, in lesioned animals(C) remained unchanged as compared to unstressed-lesioned animals. In the stressed groups, adrenal C contents were below those found in unstressed rats. beta-receptors affinity, in all the experimental groups, was similar, but VCS sham-lesioned animals underwent a significant increase in cardiac D-adrenergic receptors density when compared with basal and lesioned groups (P < 0.001). Our findings would demonstrate that the increment in cardiac beta adrenoceptors density appears as a consequence of the increase in ACTH, plasma corticosterone and sympathetic response provoked by chronic stress situations. ADTN lesion attenuated this hipophisoadrenal system response to chronic stress as well as the above mentioned cardiac beta adrenoceptors density increment.

In this article we present an overview of some peptides extracted and purified from the venom of marine snails of the genus Conus. These active peptides named conotoxins can be used as research tools to target voltage-gated ion channels as well as ligand-gated receptors. Because of their relatively small size, conotoxins can be chemically synthesized and made widely available. In this review we focus on conotoxins that target voltage-sensitive sodium channels, voltage-dependent calcium channels and nicotinic acetylcholine receptors of the vertebrate neuromuscular junction. Emphasis is given on summarizing our current knowledge of their primary structure and their specific pharmacological actions at the pre- and the post-synaptic level of the neuromuscular junction. Evidence is presented for conotoxins that discriminate between pre- and post-synaptic voltage-gated sodium channels. Among these peptides, the mu-conotoxin family is well characterized by its ability to block selectively sodium channels in skeletal muscle fibres without affecting axonal and nerve terminal Na+ channels. Furthermore, new conotoxins like Conus consors toxin (CcTx) and conotoxin EVIA selectively target Na+ channels in axons and nerve terminals without affecting skeletal muscle fibres. omega-conotoxins known as highly potent and selective blockers of voltage-sensitive calcium channels have proven to be valuable in determining the roles of the various subtypes of channels involved in acetylcholine release from motor nerve endings. Finally, Conus peptides which act at muscle nicotinic acetylcholine receptors constitute the most extensive characterized family of conopeptides that exhibit sequence similarity, different structural motifs and surprising diversity in their competitive and non-competitive actions.

In this review main hormones involved in development and muscle growth are shown with special emphasis on growth hormone (GH) and insulin-like growth factors (IGF). Chemist composition, synthesis place, action way and main action mechanisms of these hormones are reviewed. Nutritional factors which modified seric metabolites, and their effects on hormone secretion are detailed. It was observed that GH, IGF, thyroid hormones, insulin, glucocorticoids and sexual steroids act in a complex and cordinated way to produce a productive response to different> nutritional strategies.

It has been postulated that the provision of iron to the erythroid cells is under the control of a fraction of free intracellular iron. Variations in the size of this pool would send messages to either seric or cellular iron receptors aimed to keep a balance between the offer and the demand by the cells. The possibility that cell membrane receptors could be affected by chronic malnutrition was explored in these studies by the changes of iron uptake capacity of circulating mouse reticulocytes cause by the incubation of the cells with serum of either normal or anemic patients plasma donors. The results show that the incubation with nutritional anemic serum caused a significant drop in iron uptake capacity of the cells. The mechanism of the difference is discussed.

A simple in vivo bioassay suitable for routine testing of quality control of recombinant human erythropoietin (rHu-EPO) analogues was developed. Mice made polycythemic by intraperitoneal injection of 1.2 ml of a 80% suspension of heterologous (rat) red cells were used as assay animals and splenic 59Fe uptake as expression of the response to rHu-EPO. The assay took three days and the following schedule is proposed: 1) intraperitoneal injection of 1.2 ml of washed packed red cells obtained from donor rats, 2) subcutaneous injection of test material 4-5 h after transfusion, 3) intravenous administration of 59Fe tracer 48 h later, and 4) determination of splenic isotope uptake 6 h after injection. This method for the in vivo bioassay of rHu-EPO analogues is an economical and reliable alternative to the existing bioassays of the hormone.

The specific activity of long-chain acyl-CoA synthetase in microsomes from various tissues of control and calcium-deficient rats was determined. It was found that the saturated acids, palmitic and stearic, were preferential substrates compared to the non-saturated linoleic, alpha-linolenic and eicosa-8,11,14-trienoic acids. All of them showed similar Vm values with different affinity constants. After 60-day treatment on a calcium-deficient diet (0.5 g Ca/Kg diet), a significant increase in the acyl-CoA synthetase activity was observed for all the tested fatty acids in liver and kidney microsomes. These changes were evoked without any modification in the substrate selectivities shown for the control microsomes, and they were well-correlated with calcium level in both tissues. Under the calcium deficient state an increase in Vm values was observed for palmitic and eicosatrienoic acids with no changes in the corresponding Km, suggesting an increment in the number of active enzyme molecules within the microsomal membrane.

An experimental model in rats was evaluated to differentiate the effects between Copper deficiency and Molybdenosis. Sixty weaning rats (30 male and 30 female) received a diet with 70% complete powder milk (1 ppm Cu) and 30% maize meal (0.8-1.5 ppm Cu). Three experimental groups received the following mineral supplementation: copper deficiency (40 ppm Fe), molybdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) and control (40 ppm Fe + 40 ppm Cu). The animals were weighed each 14 days. At 70 days of treatment were sacrificed. Blood and liver were sampled for analyzing hematocrit, ceruloplasmin activity and Cu and Mo liver concentration. Copper deficiency group had less serum ceruloplasmin activity. Cu and Mo liver concentration were higher in the animals with molybdenosis. We concluded that when Cu levels are higher than minimum requirement, feeding with high Mo, do not affect ceruloplasmin activity. In addition, high Mo liver concentration allows us to elucidate effects "per se" of molybdenosis.