Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of crotoxin, the neurotoxic complex from the venom of the South American rattlesnake Crotalus durissus terrificus on mammalian autonomic neuromuscular transmission, have been investigated. In the longitudinal muscle of the guinea-pig ileum, crotoxin induced a dose-dependent contraction which was followed by relaxation, in spite of the continued presence of the toxin. The contractile response was inhibited by indomethacin, tetrodotoxin, verapamil or nifedipine, but was unaffected by atropine, propranolol, mepyramine or methysergide. In addition, crotoxin caused a presynaptic inhibition of the electrically-evoked twitch of the longitudinal muscle of the guinea-pig ileum. In the guinea-pig vas deferens crotoxin also caused an inhibition of the response to field stimulation. The inhibition was reversible after washing and the preparation remained insensitive to further doses of the toxin. The inhibitory effects of crotoxin were not mediated by noradrenaline and were not due to a non-specific smooth muscle depression, because it was not associated with any reduction in motor responses to acetylcholine, ATP, bradykinin or substance P. Pre-incubation of the guinea-pig vas deferens with indomethacin blocked the inhibitory effects of the toxin. This suggests that the presynaptic activity of crotoxin in the vas deferens might be mediated by prostaglandins.
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PMID:Effects of crotoxin on autonomic neuromuscular transmission in the guinea-pig myenteric plexus and vas deferens. 300 84

A total of 192 patients with active sarcoidosis of the stages I and II were examined. The state of the kinin system of the blood was studied on the basis of the values of the rate of kininogenesis and kinin-destroying activity of the blood. The rate of kininogenesis was assessed by the content of kininogen and prekallikrein in the blood and by kallikrein activity. Antikinin potential was measured by the values of the activity of carboxypeptidase N (KI), angiotensin-converting enzyme (ACE) and total kininase activity (TKA) of the blood. KI and ACE were estimated by the rate of hydrolysis of synthetic substrates, TKA was estimated biologically by inactivation of the native substrate bradykinin. In sarcoidosis patients activation of the kinin system is detected which at early stages of the disease is accompanied by stimulation and later by depression of TKA. No correlation is found between values of KI, ACE and TKA. Possible mechanisms of these disturbances detected are discussed.
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PMID:Comparative study of kinin destroying activity of blood enzymes in respiratory sarcoidosis patients. 301 25

The multisystem involvement in acute pancreatitis (AP) is a reflection of the pancreatic gland's capacity to produce a number of potent vasoactive peptides, hormones, and enzymes. The various prognostic criteria are early evaluations of these metabolic derangements. The pathogenesis of hypocalcemia, long recognized as an indicator of severity of AP, is multifactorial. Imbalances of parathyroid hormone (PTH)-calcitonin, the interactions of glucagon, gastrin and other pancreatic hormones with PTH-calcitonin, the role of free fatty acids in binding serum calcium with albumin, and the translocation of calcium ion in muscles and liver, have been recently described but remain conflicting theories. Yet, the time-honored theory of calcium-soap formation enjoys wide acceptance. Hyperglycemia, hypoglycemia, and occasional ketoacidosis in acute pancreatitis have been studied thoroughly. The complex cause-and-effect relationship between hyperlipidemia with acute pancreatitis needs further study. The coagulation abnormalities seem to be initiated by activated trypsin, and their role in microvascular coagulation appears to form a unifying hypothesis for major organ dysfunction, but this requires further investigation. Adult respiratory distress syndrome may be the result of active enzymes that digest pulmonary surfactant and/or microvascular thrombosis. The depression of cardiac function and shock are suspected to be secondary to vasoactive peptides such as bradykinin, or myocardial depressant factor, whose structure has yet to be elucidated. The renin-angiotensin alterations and renal complications in acute pancreatitis have received scant attention in the literature. The onset of moderate visual disturbances, or even blindness, in a patient with acute pancreatitis as a result of retinal vessel thrombosis is fortunately uncommon. Rare but interesting are the manifestations such as subcutaneous fat necrosis, arthralgia, and pancreatic encephalopathy. Despite the extensive literature on the complexities of the pathogenesis of complications of acute pancreatitis, there have been very few advances in the prevention and management of specific complications. It is hoped that further work on modification of enzymatic disturbances induced in acute pancreatitis will result in its effective treatment and prevention of serious complications.
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PMID:Systemic complications of acute pancreatitis. 328

Previous work in this and other laboratories has demonstrated that captopril exacerbates the hypotension produced in dogs by endotoxin. This depressor effect of captopril could result from the potentiation of bradykinin (BK) or inhibited formation of angiotensin II (AII). Anesthetized adult mongrel dogs were used in the current study. In each, the right femoral vein and artery were cannulated for the administration of drugs and monitoring of arterial pressure. A tracheostomy was performed, and the animal was respired with room air. It was found that after injection of endotoxin, AII receptor blockade (Sar1, Ile8-AII) produced a mean arterial pressure (MAP) response statistically similar to that elicited by captopril in combination with endotoxin. Although these results indicate no production of BK, the possibility of BK receptor inactivation during endotoxin shock cannot be disregarded. Additional studies suggested that in the dog, injections of BK can augment the depression of MAP caused by endotoxin and that this further depression can be prolonged by captopril. On the basis of these results, it can be concluded that in the early phases of canine endotoxin shock, AII plays a significant role in the maintenance of MAP and that BK is not produced in quantities sufficient to lower MAP.
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PMID:Bradykinin does not contribute to hypotension in early canine endotoxemia. 332 4

The purpose of the present study was to examine the pial arteriolar diameter and evoked vascular responses after single episodes of cortical spreading depression (CSD) in rats and cats in order to elucidate the mechanisms of the persistent change of cortical perfusion which succeeds CSD. This problem is of potential clinical interest also since CSD may be involved in migraine pathophysiology. Using an open cranial window technique, pial arteriolar diameters were measured with an image splitting method. Vascular reactivity was tested by local perivascular microapplication of mock cerebrospinal fluid (CSF) containing high and low levels of K+, high and low pH, adenosine and bradykinin before and after CSD which was triggered by intracortical injection of KCl. During CSD a monophasic vasodilatation of 26.0 +/- 3.7% (mean +/- S.E.M.; cat) or 64.6 +/- 3.9% (rat) was observed. Following CSD, the cat developed persistent vasodilatation (16.7 +/- 1.9%) while the rat exhibited vasoconstriction (12.1 +/- 1.8%). Both species displayed a severely impaired responsiveness to constrictor and dilating stimuli as compared to pre-CSD values. The responses were reduced by 28-84%, dependent on the substance tested. It is concluded that vascular reactivity is severely impaired after CSD (15-75 min) and that this might explain the impaired coupling between flow and metabolism after CSD.
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PMID:Change of cerebrovascular reactivity after cortical spreading depression in cats and rats. 360 27

1. When applied directly to the brain, angiotensin II amide, as either the valine(5) octapeptide, causes rats in normal fluid balance to drink water.2. The drinking response to angiotensin injections is copious, rapid, repeatable within the same test session, and stable over months of testing in the same animal.3. The response is motivationally potent and specific. After injection the animals move directly to the source of water and drink. There is typically no preliminary hyperactivity or subsequent depression. The animals do not eat, gnaw or exhibit other behaviours that are not normally seen during spontaneous drinking. The injections rouse sleeping animals to drink and interrupt eating in animals deprived of food for two days.4. The region of the brain that is most sensitive to angiotensin includes the anterior hypothalamus, the preoptic region, and the septum including the nucleus accumbens.5. Intracranial renin elicited drinking. Bradykinin and vasopressin did not, nor did adrenaline, noradrenaline or aldosterone. In the most sensitive region, sites positive for angiotensin also yielded drinking to carbachol.6. Responses were obtained with 5 ng (ca. 5 p-mole) and occurred reliably with 50 ng angiotensin or more. The dose-response curve for amount drunk rose from 5 to 100 ng and levelled off thereafter. Angiotensin is therefore the most potent dipsogen known and is effective at doses that are reasonably within the concentration range for circulating endogenous angiotensin.7. Injections into the sensitive region of doses of angiotensin that were effective for drinking did not produce peripheral haemodynamic changes in lightly anaesthetized rats.8. This work strengthens the suggestion that angiotensin is a natural hormone of drinking behaviour that participates in extracellular thirst by its release from the kidney and subsequent direct action on a specific chemoreceptive region in the anterior diencephalon and limbic lobe.
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PMID:Drinking induced by injection of angiotensin into the rain of the rat. 432 23

1. Under certain conditions D-lysergic acid diethylamide (LSD), 10(-9)-10(-6) g/ml., exerted an immediate, prolonged and slowly reversible inhibitory effect upon the post-ganglionic motor transmission in desheathed guinea-pig vas deferens preparations.2. The most critical factor influencing this action of LSD appeared to be the train length. With short trains of less than 4 or 5 pulses the twitch inhibition produced by LSD was often total. With longer trains (5-20 pulses), the degree of inhibition declined with increase in train length. These results suggest the existence of two components in the motor response to post-ganglionic stimulation, distinguished by their susceptibility to LSD.3. The inhibition of the LSD-susceptible component was related to the dose of LSD in the range 10(-9)-10(-6) g/ml., reaching a maximum at 0.5-1 x 10(-6) g/ml. The response remnants elicited by trains of more than 5 pulses under these conditions could not be reduced further by a ten- to twenty-fold increase in LSD concentration to 10(-5) g/ml. and were in fact slightly potentiated.4. The inhibition of post-ganglionic motor transmission by LSD was not explicable on the basis of an alpha-adrenoceptor blockade because it was not associated with any reduction in motor responses to noradrenaline.5. The use of propranolol excluded mediation of the LSD-inhibition by beta-adrenoceptors.6. The LSD effect was not due to a non-specific smooth muscle depression because it was not associated with any reduction in motor responses to acetylcholine, ATP or bradykinin.7. The inhibitory effect of LSD on post-ganglionic transmission resembled that of noradrenaline in that it was antagonized by phentolamine; another alpha-adrenoceptor blocking agent, phenoxybenzamine, was less effective than phentolamine in this respect.8. The LSD-inhibition was obtained in preparations taken from reserpinized guinea-pigs.9. The inhibition of motor transmission in the vas deferens by LSD was confirmed in rats, Meriones shawii and rabbits.10. The inhibition of post-ganglionic transmission by LSD was unrelated to its ability to antagonize 5-hydroxytryptamine (5-HT), to which the longitudinal muscle of the guinea-pig vas deferens is insensitive. The more potent 5-HT antagonists, methysergide and BOL 148 were either virtually inactive or considerably weaker than LSD.
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PMID:An inhibition of post-ganglionic motor transmission in the mammalian vas deferens by D-lysergic acid diethylamide. 435 65

1 The effects of 5-hydroxytryptamine (5-HT) on ganglionic transmission and on intrinsic modulation of transmission have been re-examined and compared with the effects of bradykinin by means of electrophysiological techniques.2 Early facilitation, which is maximal 40-75 ms after a conditioning stimulus, was considerably enhanced by 5-HT. This enhancement was concentration-dependent, the threshold concentration lying between 0.1 and 1 muM. With concentrations of 5-HT 10 muM or greater, there was some depression of the Sa response to the conditioning stimulus.3 5-HT reduced or abolished the inhibition of a test response induced by a conditioning response 100-300 ms earlier. Facilitation was observed at these intervals at concentrations of 5-HT of 25 muM or greater.4 Late facilitation, which is maximal 700-2000 ms after a conditioning stimulus, was increased by 5-HT, but the effect was not as great as on early facilitation and was not always seen with a concentration of 1 muM.5 Bradykinin reduced early facilitation but increased the amplitude of the transmitted action potential in response to a single stimulus. The threshold concentration producing these effects was between 1 and 2 muM.6 5-HT produced a rapid depolarization of the ganglion cell membrane which was followed by an after-hyperpolarization.7 Bradykinin either produced no measurable change in ganglion cell resting potential or only very small, transient depolarizations.8 The depression of transmission, enhancement of intrinsic facilitation and the depolarization of the ganglion cell membrane induced by 5-HT may indicate more than one mode of action of this amine at the ganglionic synapse.
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PMID:The facilitatory actions of 5-hydroxytryptamine and bradykinin in the superior cervical ganglion of the rabbit. 437 29

1. The actions of acetylcholine, carbachol, methacholine, pilocarpine, nicotine, tetramethylammonium, 1,1-dimethyl-4-phenylpiperazinium, histamine, 5-hydroxytryptamine, angiotensin, bradykinin and potassium chloride were investigated on the sensory endings of the rabbit saphenous nerve.2. By means of specific antagonists the presence of separate receptor sites sensitive to acetylcholine, histamine, 5-hydroxytryptamine and bradykinin were demonstrated.3. The cholinoceptive receptors were shown to be predominantly nicotinic, but there was evidence of the existence of at least a small population of muscarinic receptors.4. Catecholamines of both alpha and beta types exhibited some stimulatory activity on administration. It is unlikely that this was due to either vasomotor effects or to any action involving the arrectores pilorum muscles.5. The alpha-receptor stimulants modified the response to acetylcholine in a biphasic way. There was a brief enhancement of effect followed by a more prolonged depression. beta-receptor stimulation only produced a prolonged enhancement of acetylcholine-evoked activity.6. The discharge generated by acetylcholine was augmented by anticholinesterases and blocked by ganglion blocking agents. None of these drugs in reasonable doses affected the response to stroking the fur. The results therefore support earlier evidence against a sensory cholinergic synaptic link.
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PMID:Drug receptor sites in the rabbit saphenous nerve. 439 78

Several important vasoactive substances are taken up and/or metabolized during a single transpulmonary passage. Such substances include 5-hydroxytryptamine, prostaglandins (PGs) of the E and F series, and peptide substrates (angiotensin I and bradykinin) for angiotensin-converting enzyme (ACE). When these metabolic processes are altered, predictable changes in systemic hemodynamics can follow because of altered arterial concentrations of the vasoactive substances. For example, a single dose of captopril (2 mg/kg, i.v.) given to conscious rabbits caused prolonged depression in pulmonary ACE activity, an effect that coincided with a significant reduction in mean systemic arterial pressure. In another study, total cardiopulmonary bypass in anesthetized dogs was associated with a time-dependent increase in arterial levels of immunoreactive PGE. Coincident with this elevation in PGE was a significant decrease in total systemic vascular resistance. The decrease in resistance was inhibited by pretreatment with indomethacin or by maintaining lung perfusion during extracorporeal circulation (i.e., left heart bypass). Thus, in the intact animal, significant reduction in lung metabolism, induced by either pharmacological or other experimental means, may modify vasoregulation of peripheral circulation. Furthermore, measurement of these metabolic functions may provide biochemical information about the pulmonary microcirculation, which is both the locus of these activities and an early site of acute lung injury.
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PMID:Metabolic functions of the lung and systemic vasoregulation. 608 8


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