Action Of Epinephrine Research Articles

Effect of aqueous solution of stevioside on pharmacological properties of some cardioactive drugs.

Stevioside is a glycoside that supposedly possesses a number of pharmacodynamic effects such as anti-infective, hypoglycemic, along with the beneficial influence on the cardiovascular system. The aim of this study was to determine the effect of rats pretreatment with aqueous solution of stevioside on pharmacological actions of adrenaline, metoprolol and verapamil. Rats were administered (intraperitoneally 200 mg/kg/day) stevioside as aqueous solution or physiological saline in the course of 5 days, then anaesthetized with urethane and the first ECG recording was made. The prepared jugular vein was connected to an infusion pump with adrenaline (0.1 mg/mL), verapamil (2.5 mg/mL) or metoprolol (1 mg/mL). Control animals, pretreated with saline, in addition to the mentioned drugs, were also infused with the solution of stevioside (200 mg/mL) in the course of recording ECG. The infusion of stevioside produced no significant changes in ECG, even at a dose exceeding 1,600 mg/kg. In the control group, a dose of adrenaline of 0.07 +/- 0.02 mg/kg decreased the heart rate, whereas in the stevioside-pretreated rats this occurred at a significantly higher dose (0.13 +/- 0.03 mg/kg). In stevioside-pretreated rats, the amount of verapamil needed to produce the decrease in heart rate was significantly lower compared to the control. The pretreatment with stevioside caused no significant changes in the parameters registered on ECG during infusion of metoprolol. The results suggest that pretreatment with stevioside may change the effect of adrenaline and verapamile on the heart rate.

Antiypertensive action of ethanolic extract of Imperata cylindrica leaves in animal models.

This work was carried out to determine antihypertensive effect of ethanolic extract of Imperata cylindrical leaves using cat and rabbit models. A freeze dried 70% ethanolic extract was prepared and increasing concentrations from 10 to 320 mg/ml were administered in vivo to anaesthetized cats and in vitro to rabbit jejunum. Adrenaline and phentolamine were used as control drugs. The extract exhibited a significant dose-dependent reduction in amplitude of contraction of smooth muscle cells of rabbit jejunum in comparison with standard antihypertensive drug, adrenaline. The heart pressure of the cats was significantly reduced with 160 and 320 mg/ml of the extract from 266 to 180 mmHg (p = 0.012) but there was no effect on the heart rate. The minimum effective dose EC50 was 0.013. Ethanolic leaf extract of I. cylindrica exhibited vasodilative antihypertensive properties similar to mechanism of action of adrenaline. The extract could be used to manage hypertension. Key words: Imperata cylindrical, antihypertensive, ethanolic extract, β-blockers.

Influx of Ca2+ via Cav1.3 calcium channels in satellite cells of muscle fibers in rats

Voltage-dependent L-type Cav1.3 channels have been detected in satellite cells localized to muscle fibers. It was established that the action of carbachol, which activates nicotinic acetylcholine receptors and causes cell membrane to depolarize, resulted in the activation of these channels. In addition, verapamil and amlodipine, selective L-type calcium channel blockers, suppressed extracellular calcium influx into the cytoplasm. It was noted that in a calcium-free medium, carbachol had no influence on the concentration of calcium in the cytoplasm of satellite cells, whereas adrenaline induced calcium efflux from intracellular stores. In addition, calcium influx into the cytoplasm was not suppressed by verapamil and amlodipine under the action of adrenaline and noradrenalin in a medium with calcium, and an ICI- 118551 blocker of β2-adrenoreceptros significantly decreased the increase in the concentration of calcium in the cytoplasm.

In this issue – April 2013

In this issue – <scp>A</scp>pril 2013

Duration of action of a topical anaesthetic formulation for pain management of mulesing in sheep

To investigate the effect of topical anaesthesia on 'mothering up' of lambs after mulesing and marking, and for pain alleviation over a 24-h period. Two separate trials were performed on Merino lambs undergoing the mules procedure for flystrike prevention, to assess the efficacy of immediate postoperative topical anaesthetic wound dressing containing lignocaine (hydrochloride) 40.6 g/L, bupivacaine (hydrochloride) 4.5 g/L, adrenaline (tartrate) 24.8 mg/L and cetrimide 5.0 g/L in a gel base (Bayer Animal Health, Gordon, NSW, Australia). In both trials, lambs were assigned to one of three treatment regimens: control, mules procedure with topical anaesthetic (0.5 mL/kg) and mules procedure without topical anaesthetic treatment. Parameters measured included body weight, assessment of skin and wound sensitivity to light touch and pain stimulation, behavioural responses and time to mother up and to feed. In both trials there was rapid (1 min) and prolonged (up to 24 h) wound analgesia as shown by lower scores for light touch (P<0.001) and pain responses (P<0.001), with absent or significantly diminished primary and secondary hyperalgesia (P≤0.05) and significant reduction in pain-related behaviours (P<0.001) in treated versus untreated lambs. Significant pain alleviation and improved recovery can be achieved in lambs for at least 24 h after mulesing through the use of topical anaesthesia. It is suggested that the haemostatic action of adrenalin, together with inhibition of the inflammatory cascade and the barrier effect of the gel within the product, may explain the prolonged anaesthesia up to 24 h observed in the present study. These results suggest that topical anaesthesia has the capacity to dramatically improve the welfare of lambs undergoing mulesing.

Physiologic implications of inter-hormonal interference in fish: Lessons from the interaction of adrenaline with cortisol and thyroid hormones in climbing perch (Anabas testudineus Bloch)

Adrenaline and cortisol, the major stress hormones, are known for its direct control on stress response in fish. Likewise, as an important stress modifier hormone, thyroid hormone has also been implicated in stress response of fish. We tested whether the hypothesis on the phenomenon of inter-hormonal interference, a process that explains the hormonal interactions, operates in fish particularly between adrenaline, cortisol and thyroid hormones. To achieve this goal, indices of acid–base, osmotic and metabolic regulations were quantified after adrenaline challenge in propranolol pre-treated air-breathing fish (Anabas testudineus). Short-term adrenaline (10ngg−1) injection for 30min produced a rise in plasma cortisol without affecting plasma T3 and T4. On the contrary, blocking of adrenaline action with a non-selective blocker, propranolol (25ngg−1) for 90min reduced plasma cortisol along with plasma T4 and that indicate a possible interference of these hormones in the absence of adrenaline challenge. Similarly, a reduction in plasma T3 was found after adrenaline challenge in propranolol pre-treated fish and that suggests a functional synergistic interference of adrenaline with T3. Adrenaline challenge in these fish, however, failed to abolish this propranolol effect. The remarkable systemic hypercapnia and acidosis by propranolol pre-treatment were reversed by adrenaline challenge, pointing to a direct action of adrenaline on acid–base indices probably by a mechanism which may not require β-adrenergic receptor systems. Interestingly, the prominent adrenaline-induced hyperglycemia, hyperlactemia and hyperuremea were not altered by propranolol treatment. Similarly, adrenaline challenge promoted and propranolol reduced the osmotic competencies of the gills, kidneys and liver of this fish as evident in the sodium and proton pump activities. The modified physiologic actions of adrenaline and its modified interaction with THs and cortisol in blocked fish indicate an interaction of adrenaline with cortisol and THs. Our physiologic evidences thus support the hypothesis of the phenomenon of inter-hormonal interference.

O leucograma como indicador de estresse no desmame e no transporte rodoviário de bovinos da raça Nelore

Stress can cause economic losses due to lower weight gain and increased susceptibility of animal diseases. Among the events that cause stress in calves, stand out weaning and road transport, which can result in increased serum concentrations of adrenaline and / or cortisol. This study evaluated the influence of weaning and road transport on the leukogram of Nelore calves. With this purpose, 30 calves with seven to eight months of age, divided into three groups, the first being composed of lactating animals (GL), the second by weaning animals (GD) and the third by weaning animals subjected to road transport for four hours (GDT). The first day of weaning, but not in subsequent days, there were changes in GD and GDT leukogram compatible with the action of adrenaline, as significant increases counts of WBC and neutrophils (p &lt; 0.05), without changing in the neutrophil lymphocytes ratio (NL). In the GDT, immediately after transport, but not in subsequent days, leukogram changes were (p &lt; 0.05) compatible with the action of cortisol, as higher N: L ratio and decreased eosinophil count. It was concluded that, under the conditions of this experiment, there are changes in leukocytes on weaning and road transport related to the action of adrenaline and road transport, respectively, and that the WBC can be used as an indicator of stress in this species.

Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α(2)-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.

G PROTEIN‐COUPLED RECEPTORS

The invention provides human G-protein coupled receptors (GCREC) and polynucleotides which identify and encode GCREC. The invention also provides expression vectors, host cells, antibodies, agonists, and antagonists. The invention also provides methods for diagnosing, treating, or preventing disorders associated with aberrant expression of GCREC.

Role of β3-adrenoceptors in regulation of retinal vascular tone in rats

The aim of this study was to determine the role of β(3)-adrenoceptors in the action of endogenous catecholamines (adrenaline and noradrenaline) on rat retinal arterioles in vivo. Using an original high-resolution digital fundus camera, the rat ocular fundus images were captured. The diameter of retinal arterioles contained in the images was measured. Both systemic blood pressure and heart rate were recorded continuously. Adrenaline (0.3-5.0μg/kg/min, i.v.) increased the diameter of retinal arterioles, mean blood pressure and heart rate in a dose-dependent manner. Under blockade of β(1)/β(2)-adrenoceptors with propranolol (2mg/kg, i.v. bolus followed by 100μg/kg/min infusion), adrenaline decreased the diameter of retinal arterioles. Similar observation was made under treatment with the β(3)-adrenoceptor antagonist L-748337 (50μg/kg, i.v.). The pressor response to adrenaline was enhanced by propranolol, but not by L-748337. The positive chronotropic action of adrenaline was markedly prevented by propranolol, whereas it was unaffected by L-748337. Noradrenaline (0.03-1.0μg/kg/min, i.v.) decreased the diameter of retinal arterioles but increased the mean blood pressure and heart rate. The effects of noradrenaline on retinal arteriolar diameter and blood pressure were unaffected by propranolol or L-748337. The positive chronotropic action of noradrenaline was almost completely abolished by propranolol. These results suggest that β(3)-adrenoceptors play crucial roles in vasodilator responses to adrenaline of retinal arterioles but have minor or no effect on noradrenaline-induced responses. The results also indicate that the functional role of β(3)-adrenoceptors may be more important than that in peripheral resistance vessels.

Effect of alimentary deprivation on quantitative and time characteristics of nutrition of the goldfish in norm and under action of adrenalin

Effects of the intraperitoneally administered adrenalin (0.14 mg/kg) on volume and time characteristics (duration) of the individual, grouped, and summarized nutrition was studied in goldfish Carassius auratus (L.) previously kept on normal and restricted (for 10 and 15 days) ration. The fish on restricted ration demonstrated the two-phase alimentary response to the adrenalin injection similar with that in normally feeding fish: a decrease in volume and in the grouped and summarized duration of nutrition in the first phase of the hormone action and an increase-in the second phase; however, the value of the effect in the first phase was lower, while in the second phase-higher than in the fish that obtained before the experiment the sufficient amount of food. Duration of individual nutrition increased in all fish groups, including the control one, the maximal increase being observed in goldfish submitted to alimentary deprivation. The content of glycogen in hepatopancreas of the normally fed goldfish by the end of experiment exceeded that in fish restricted in nutrition 4.5–6 times. The obtained results confirm the suggestion that a decrease of level of reserved substances in the body leads to reduction of susceptibility of fish to the stress hormoneadrenalin and, hence, to a change of the value of its effects on the goldfish food-procuring activity, with preservation of dynamics of parameters.

Short-term effects of palmitate and 2-bromopalmitate on the lipolytic activity of rat adipocytes

Aims Fatty acids are involved in the regulation of lipolysis in adipocytes; however, this regulatory action is unclear. The present study aimed to determine the short-term influence of palmitate and its non-metabolisable analogue, 2-bromopalmitate, on the lipolytic activity of adipocytes. Main methods Freshly isolated rat adipocytes were exposed to lipolytic modulators with or without palmitate or 2-bromopalmitate. Glycerol released from cells was determined as an indicator of lipolysis. Moreover, cAMP, ATP and changes in mitochondrial membrane potential were measured in cells treated with 2-bromopalmitate. Key findings It was demonstrated that glycerol release from adipocytes incubated with epinephrine alone or epinephrine with insulin was unchanged by palmitate. However, 2-bromopalmitate was found to significantly decrease lipolysis stimulated by epinephrine or dibutyryl-cAMP. The inhibitory effect of 2-bromopalmitate on lipolysis was accompanied by reduced cAMP in adipocytes. Moreover, 2-bromopalmitate diminished hyperpolarisation of the inner mitochondrial membrane. Adipocyte exposure to 2-bromopalmitate also resulted in a substantial ATP depletion. The effects of 2-bromopalmitate on lipolysis and on ATP content were prevented neither by high glucose nor by alanine in the incubation medium. Significance These findings demonstrate that short-term adipocyte exposure to palmitate disturbs neither the lipolytic action of epinephrine nor the antilipolytic action of insulin. However, 2-bromopalmitate significantly decreases lipolysis probably due to impaired metabolic activity of mitochondria.

Effects of adrenaline in human colon adenocarcinoma HT-29 cells

Aims Stress has been implicated in the development of cancers. Adrenaline levels are increased in response to stress. The effects of adrenaline on colon cancer are largely unknown. The aims of the study are to determine the effects of adrenaline in human colon adenocarcinoma HT-29 cells and the possible underlying mechanisms involved. Main methods The effect of adrenaline on HT-29 cell proliferation was determined by [ 3H] thymidine incorporation assay. Expression of cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) were detected by Western blot. Matrix metalloproteinase-9 (MMP-9) activity and prostaglandin E 2 (PGE 2) release were determined by zymography and enzyme immunoassay, respectively. Key findings Adrenaline stimulated HT-29 cell proliferation. This was accompanied by the enhanced expression of COX-2 and VEGF in HT-29 cells. Adrenaline also upregulated MMP-9 activity and PGE 2 release. Adrenaline stimulated HT-29 cell proliferation which was reversed by COX-2 inhibitor sc-236. COX-2 inhibitor also reverted the action of adrenaline on VEGF expression and MMP-9 activity. Further study was performed to determine the involvement of β-adrenoceptors. The stimulatory action of adrenaline on colon cancer growth was blocked by atenolol and ICI 118,551, a β 1- and β 2-selective antagonist, respectively. This signified the role of β-adrenoceptors in this process. In addition, both antagonists also abrogated the stimulating actions of adrenaline on COX-2, VEGF expression, MMP-9 activity and PGE 2 release in HT-29 cells. Significance These results suggest that adrenaline stimulates cell proliferation of HT-29 cells via both β 1- and β 2-adrenoceptors by a COX-2 dependent pathway.

The influence of 5-hydroxytryptamine on the actions of adrenaline

The influence of 5-hydroxytryptamine on the actions of adrenaline

THE SITE OF ACTION OF SYMPATHOMIMETIC AMINES ON THE CIRCULAR MUSCLE STRIP FROM THE GUINEA-PIG ISOLATED ILEUM.

Abstract The circular muscle strip of the isolated ileum of the guinea-pig, treated with the anticholinesterase mipafox (100 μg/ml) responds to doses of methacholine or carbachol with contractions that are inhibited by previous doses of noradrenaline, adrenaline or isoprenaline in that order of potency. Piperoxane antagonised the inhibitory action of adrenaline, but not that of aminophylline. Dichloroisoprenaline did not antagonise the action of adrenaline on the circular muscle strip. It is concluded that the site of action of the sympathomimetic amines on the circular muscle of the guinea-pig ileum is located at postganglionic neuro-effector junctions in the smooth muscle.

Pharmacological studies in the apocynaceous genus Aspidosperma Mart. & Zucc., Aspidosperma oblongum A.D.C.

Summary The bark of Aspidosperma oblongum A.DC. contains alkaloids which antagonise the actions of acetylcholine, histamine, barium and adrenaline, and reverse the actions of the latter. The alkaloids markedly depress the isolated heart's action and change the electrocardiogram pattern.

A Note on an Effect of Pyrogallol on Duodenal Motility

Abstract Pyrogallol injected intravenously exerts an initial depressor and a secondary stimulatory effect on the duodenal motility of dogs. The first effect is similar to that of adrenaline. The duodenal excitation is thought to be due to a peripheral cholinergic mechanism. Pyrogallol enhances the duration of the inhibitory action of adrenaline on duodenal motility and converts the action of histamine to an inhibition

Some pharmacological properties of a commercial heart extract.

Abstract An investigation was made of the pharmacological properties of a commercial heart extract (Recosen), said to be of value in the treatment of angina pectoris. This extract increased coronary flow but decreased force of beat in isolated perfused mammalian hearts. It potentiated the pressor effects of adrenaline in the spinal cat whilst not affecting those of noradrenaline, and it antagonised the actions of adrenaline and noradrenaline upon intestinal muscle. A mild anticholinesterase activity was demonstrated on striped muscle. The significance of these findings is discussed.

EFFECT OF PRONETHALOL ON SOME INHIBITORY ACTIONS OF CATECHOLAMINES.

Abstract On the blood pressure of the pithed rat isoprenaline produced a vasodepressor, noradrenaline a pressor, and adrenaline a biphasic response consisting of a rise followed by a fall in the pressure. The magnitude of the responses to increasing doses of adrenaline was not proportional to the doses. An intravenous injection of pronethalol (nethalide) hydrochloride (1 mg./kg.) changed the responses to adrenaline into purely pressor, well-graded responses; they were also increased. The responses to isoprenaline after pronethalol were reduced, but those to noradrenaline remained usually unaltered. Similar results were obtained in anaesthetised rats, rabbits and guinea-pigs, but the augmentation of the pressor effect of adrenaline was not so marked as in pithed rats. The vasodepressor action of dopamine in rabbits and guinea-pigs was not blocked by pronethalol (2·5 to 10 mg./kg.). The inhibitory actions of adrenaline, noradrenaline and isoprenaline on the isolated rat uterus and rabbit colon were not consistently antagonised by concentrations of pronethalol up to 1·0 μg./ml. In experiments on the rabbit duodenum and ileum, pronethalol, 0·2 to 1·0 μg./ml., reduced the relaxations produced by all three catecholamines. These results are discussed in relation to Ahlquist's theory of a dual adrenergic receptor mechanism.

Pharmacological properties of hydrallazine, dihydrallazine and some related compounds.

Abstract Hydrallazine and dihydrallazine cause adrenaline reversal and antagonise the pressor effects of noradrenaline on the cat blood pressure. Both hydrallazine and dihydrallazine antagonise vasoconstriction caused by adrenaline, noradrenaline, histamine, 5-hydroxytryptamine or barium chloride in isolated perfused preparations of the rat hind quarters or rabbit ear. In isolated aortic strips antagonism is shown to the constrictor action of adrenaline, noradrenaline, histamine and 5-hydroxytryptamine but not to barium chloride. Marked antagonism to 5-hydroxytryptamine is shown only on the perfused rat hind quarters or rabbit ear. Antagonism to pressor reflexes is of moderate potency or is absent. Applied locally to the carotid sinuses of the cat, hydrallazine causes a rise of blood pressure. Hydrallazine and dihydrallazine have mainly a peripheral site of action involving an effect upon the contractile elements of the blood vessel walls. 3-Phenyl-6-hydrazino-pyridazine HCl, 1-hydrazinoisoquinoline HCl and 3:6-dihydrazino-pyridazine nitrate appear to have similar properties to hydrallazine and dihydrallazine.