Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Autacoids”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 307 records · Page 17Linked to original sources
PubMed1995

Production of adenosine and nucleoside analogs by the exchange reaction catalyzed by rat liver adenosine kinase.

We have previously shown [8] that rat liver adenosine kinase can produce [14C]AMP from [14C]adenosine (Ado) and unlabelled adenosine monophosphate (AMP), in the absence of ATP, by an exchange reaction. In this study, we investigated whether Ado or AMP could be replaced in this exchange reaction by other nucleosides or nucleoside monophosphates (NMP), respectively. In the presence of 1 mM of the unlabelled NMP analogs 7-deazaadenosine (tubercidin) 5'-monophosphate, 6-chloropurine riboside 5'-monophosphate, or N6-methyl-AMP, [14C]AMP was formed from 20 microM [14C]Ado at up to 50% of the rate recorded with 1 mM unlabelled AMP. In the presence of 0.2 mM of the unlabelled analog nucleosides tubercidin, N6-methyladenosine, or 6-methylmercaptopurine riboside, [14C]Ado was generated from 1 mM [14C]AMP at up to 60% of the rate recorded with 0.2 mM unlabeled Ado. Small amounts of [14C]Ado were also formed from the natural nucleosides 5-amino-4-imidazolecarboxamide (AICA) riboside or 2'-deoxyadenosine. Administration of therapeutic anticancer and antiviral nucleosides that can serve as substrates for the exchange reaction catalyzed by adenosine kinase might, thus, result in a net production of Ado, a potent autacoid with physiological effects in numerous tissues.

Adenosine↗
PubMed1989

Histamine regulates the generation of human cytolytic T lymphocytes.

Human cytolytic T lymphocytes (CTL) were generated in the presence and absence of histamine in order to define the role of this autacoid in immune regulation. Histamine (10(-8)-10(-4) M) suppressed the generation of class I specific CTL but, at 10(-4) M, actually increased class II specific cytolysis. Histamine acted at the level of CTL generation; histamine was not present in the cytolytic assay. When histamine was added to the cytolytic assay with CTL grown without histamine, the lytic ability of the effector cells was similar to that of controls. Histamine-induced suppression of class I specific cytolysis was blocked by continuous culture with the H2 antagonist ranitidine but not with the H1 antagonist pyrilamine. These data suggest that suppression was mediated by the H2 receptor. Continuous culture with histamine had no effect on T cell proliferation or the expression of cell surface molecules. Histamine-induced suppression of class I specific cytolysis was reversed by the addition of PHA to the cytotoxicity assay, showing that the cytolytic machinery was intact. These data provide evidence that histamine is involved in regulation of cytolytic T cells.

Antibodies, Monoclonal↗
PubMed1979

Prostaglandin E1-induced latent epileptogenic foci.

Suprafusion of 125 microliter 6% KCl solution over the visual cortex of rabbits 2-24 h after they suffered a prostaglandin (PG) E1-induced epileptic seizure was found to cause a recurrence of seizure activity. The initial seizure was induced by the cortical suprafusion of PGE1 over the left visual cortex of PG transport inhibitor-pretreated rabbits. Control animals that were not pretreated with PG transport inhibitors (bromcresol green or probenecid), or received suprafusion of saline or PGF2 alpha rather than PGE1, did not show initial seizure activity. In these animals, and in animals that had PG-induced seizures 72 h before KCl administration, the KCl solution caused only inhibition of the visually evoked response but no seizure activity. The results are interpreted to indicate that under appropriate conditions PGE1 can create a latent epileptogenic focus which can be reactivated by KCl. It is suggested that since PGE1 is produced by the brain normally, and in increased amounts as the result of overstimulation, irritation or trauma, this potent autacoid may play a role in the spontaneous development of latent epileptogenic foci or the recurrence of epileptic seizures.

Animals↗
PubMed1979

Anaphylaxis in guinea-pig peripheral airways in vitro.

The contributions made by histamine, prostaglandins (PG) and slow reacting substance (SRS-A) to anaphylactic contractions in isolated guinea-pig lung were investigated. Histamine, PGF2alpha and SRS-A induced isometric contractions in lung parenchymal strips and in tracheal smooth muscle. The effective concentrations of the autacoids were the same in lung strips and tracheas. Anaphylactic contractions in lung strips from bovine serum albumin sensitised animals were not affected by mepyramine (5 X 10(-6)M), or indomethacin (3 X 10(-5)M) but were markedly reduced by FPL 55712 (5 X 10(-5)M) suggesting that SRS-A plays a major role in the anaphylactic response. The effect of isoprenaline on anaphylactic histamine release and contractions was also examined. Anaphylactic contractions in lung strips were inhibited by isoprenaline (10(-10)--10(-7)M). Isoprenaline also inhibited anaphylactic histamine release from lung parenchyma. 10(-7)M isoprenaline inhibited contractions by 85.6% and reduced histamine release by 27.9%. The results suggest that histamine release does not contribute markedly to anaphylaxis in peripheral airways.

Anaphylaxis↗
PubMed1985

Activities and antagonism of bombesin on urinary smooth muscles.

Substance P (SP), bombesin (BB) and bradykinin (BK) induce dose-dependent contractions of the rat and guinea-pig urinary bladders (RUB, GPUB). The three peptides differ in their affinities and intrinsic activities, BB being the most active both in terms of affinity (pD2 8.33 in the RUB and 8.83 in the GPUB), SP (8.03 and 7.53), BK (7.20 and 7.35), and of intrinsic activity. The myotropic effects of BB and SP are not modified by antagonists of neurotransmitters and autacoids that occur in peripheral organs, but that of BK is reduced in the presence of both the cyclooxygenase and lipoxygenase inhibitors. Undeca- and octapeptide antagonist analogues of SP and SP-(4-11) show similar pA2 values against BB and SP and are inactive against BK: the compound [D-Pro4, Lys6, D-Trp7,9,10, Phe11] SP-(4-11) is however more active (pA2 6.36 in the RUB and 6.18 in the GPUB) against BB than against SP (pA2 5.33 and 5.65 respectively), while it is inactive against BK. These results confirm data from the literature as to the ability of some tachykinin-antagonists to act against BB and shows chemical modifications that can improve the antagonist potency selectively against BB.

Animals↗
PubMed1986

Different receptors are involved in the endothelium-mediated relaxation and the smooth muscle contraction of the rabbit pulmonary artery in response to substance P and related neurokinins.

Four neurokinins, substance P (SP), neurokinin A (NKA) neurokinin B (NKB) and kassinin (Kass) were used in the present study together with other peptides and nonpeptide agents to demonstrate the existence of two different neurokinin receptor types in the rabbit isolated pulmonary artery. Similar to other arterial vessels, the endothelium-dependent relaxation of the pulmonary artery in response to neurokinins is due to the activation of a SP-P receptor more sensitive to SP than to the other neurokinins. The endothelium-dependent relaxation is an indirect phenomenon, mediated by an unknown endothelial agent, similar to that released by acetylcholine. The contraction of the pulmonary artery in response to neurokinins is due to receptors of the NK-A type, particularly sensitive to NKA and NKB, and much less sensitive to SP. The contraction is a direct phenomenon, apparently not involving any of the known endogenous autacoids and neurotransmitters or metabolites of arachidonic acid. Contraction appears to be due to stimulation by the neurokinins of receptors located in the arterial smooth muscle. The results presented in this paper indicate that NK-A receptors for neurokinins (which are present in the tracheo-bronchial tree) are also to be found in pulmonary vessels and mediate contraction of arterial vascular smooth muscle, an interesting property of neurokinins.

Animals↗
PubMed1992

Suppression by cetirizine of pleurisy triggered by antigen in actively sensitized rats.

The efficacy of cetirizine in comparison with meclizine, another piperazine H1 receptor antagonist, in rat pleurisy caused by allergen or autacoid was investigated. Sensitization was achieved by subcutaneous injection of a mixture of ovalbumin and aluminium hydroxide. Fourteen days later, the animals were challenged with an intrathoracic injection of ovalbumin (12 micrograms/cavity), which caused drastic mast cell degranulation, followed by pleural oedema and leucocyte influx. Cetirizine and meclizine (2.5-30 mg/kg i.p.), 1 h before challenge, inhibited the exudatory response evoked by antigen, under conditions where neutrophil and eosinophil accumulation was affected only by the former. When administered intrathoracically 22 h after allergen, i.e. using a curative approach, cetirizine (15 micrograms/cavity) drastically reduced the pleural eosinophilia noted 24 h post-challenge, indicating that this drug can reverse an already established eosinophilia. Cetirizine (15 mg/kg i.p.) also restored, to about 39% (P < 0.001), the number of uninjured mast cells recovered from the pleural cavity following allergen stimulation. In normal rats, cetirizine (5-15 micrograms/cavity) completely inhibited the pleural exudation elicited by histamine and only partially the exudation caused by 5-hydroxytryptamine or bradykinin, but was quite inactive against platelet-activating factor. We conclude that the pleural exudation triggered by allergen, vasoactive amines or bradykinin is clearly sensitive to cetirizine. In addition, the ability of the drug to interfere with pleural neutrophil or eosinophil mobilization and mast cell degranulation seems not to be associated with its ability to block the histamine H1 receptor.

Animals↗
PubMed1984

Species differences in the responses of the eye to irritation and trauma: a hypothesis of divergence in ocular defense mechanisms, and the choice of experimental animals for eye research.

Information published during the past century, especially the last decade, has identified pronounced species differences, not only in the morphological organization of ocular structures, but also in the functional responses of the eyes of different mammals to experimental and surgical procedures, as well as to drugs and autacoids. For the most part, these differences have been regarded as peculiarities or weakness rather than as fundamental evolutionary adaptations optimally suited to the environment and behavior of each species. This paper proposes a working hypothesis of evolutionary divergence in ocular defense mechanisms, based on some of the known morphological and functional differences among mammals, and discusses the implications of these differences with regard to the choice of appropriate animals for use as models in different areas of ophthalmic research.

Aging↗
PubMed1991

The biology of beta-adrenergic receptors: analysis in human epidermoid carcinoma A431 cells.

1. G-protein-linked transmembrane signaling has emerged as a major pathway for information transduction across the cell membrane. 2. In addition to photopigments that propagate the signal from light, cell-surface receptors for hormones, neurotransmitters, and autacoids propagate signals from ligand binding to membrane-bound effector units via G-proteins. 3. Biochemical and molecular features of one prominent member of these receptors, the beta-adrenergic receptor, will be highlighted in the present article. 4. The role of the human epidermoid carcinoma A431 cells as a model for the study of the structure and biology of beta-adrenergic receptors will be emphasized. 5. A model for receptor regulation, gleaned from recent advances in the biochemistry, cell and molecular biology of beta-adrenergic receptors, is discussed.

Amino Acid Sequence↗
PubMed1992

Inhibition by angiotensin converting enzyme inhibitors of endothelin secretion from cultured human endothelial cells.

We conducted a study to determine whether angiotensin converting enzyme inhibitors (ACEIs) inhibit endothelin secretion from cultured human endothelial cells. Confluent umbilical vein endothelial cells were incubated in multi-well plates with culture medium containing either captopril (10(-6), 10(-5), 10(-4) M) or enalaprilat (10(-7), 10(-6), 10(-5) M) for 6 hours. Immunoreactive endothelin in the medium was measured by radioimmunoassay. Calf serum (CS) stimulated endothelin release in a concentration-dependent manner, and both ACEIs inhibited 5% CS-stimulated endothelin release in a concentration-dependent manner. To explore the mechanisms of ACEI-induced suppression of endothelin release, the effects of angiotensin II (10(-8), 10(-7), 10(-6) M), angiotensin converting enzyme (0.1, 1, 10 mU/ml), bradykinin (10(-8), 10(-7), 10(-6) M), and sodium nitroprusside (10(-6), 10(-5), 10(-4) M) on endothelin release were also examined. Although angiotensin II and angiotensin converting enzyme had no significant effect on endothelin release, concentration-dependent suppression occurred with bradykinin and sodium nitroprusside. These results indicate that ACEIs inhibit the stimulated release of endothelin from human endothelial cells, and provide indirect evidence that ACEI-induced ET suppression may be mediated via potentiation of autacoid formation from the cells.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1983

Effects of captopril and propanolol on bradykinin-induced changes in vascular pressures, lymph total protein concentration, and weight in canine forelimbs.

Sixty-minute local intraarterial infusions of bradykinin (0.8, 5, or 10 micrograms base/min) produced transient forelimb vasodilation and dose-related increases in lymph flow, lymph total protein concentration, total protein transport, and weight in forelimbs perfused at a controlled flow rate. Mean aortic pressure was not affected by these infusion rates of bradykinin. Following pretreatment with captopril, the local intraarterial infusion of these same doses of bradykinin produced sustained systemic hypotension. The increase in protein efflux and edema formation produced by local infusions of bradykinin following pretreatment with captopril was markedly increased during the infusion of the low dose of bradykinin (0.8 micrograms base/min, ia), but was attenuated during the local infusion of the larger dose of bradykinin (5 micrograms base/min, ia). Following pretreatment with both captopril and propranolol, the increase in protein efflux and edema formation produced by this larger dose of bradykinin (5 micrograms base/min) was greater than that produced by infusions of this dose of bradykinin alone or after pretreatment with captopril. Moreover, the increase in protein efflux and edema formation was greater during the infusion of the higher dose of bradykinin than during the infusion of the low dose of this autacoid under these conditions. The 60-min infusion of a massive dose of bradykinin into the left ventricular chamber (280 micrograms base/min) produced sustained decreases in aortic and forelimb perfusion pressure, but little edema formation relative to that produced by local intraarterial infusions of this agent. In contrast, the 60-min intravenous infusion of only 5 micrograms base/min of bradykinin following pretreatment with both captopril and propranolol produced profound systemic hypotension and marked increases in protein efflux and edema formation in forelimbs perfused at a controlled flow rate comparable to that produced by the local intraarterial infusion of this dose of bradykinin alone. These data demonstrate that endogenous kininases and catecholamines may dramatically affect the increase in protein efflux and edema formation produced by either local or systemic infusions of bradykinin by modulating the magnitude of the increase in macromolecular permeability.

Animals↗
PubMedDate not supplied

Snake venoms in science and clinical medicine. 1. Russell's viper: biology, venom and treatment of bites.

Russell's viper, Vipera russelli (Shaw), is distributed erratically in 10 south Asian countries and is a leading cause of fatal snake bite in Pakistan, India, Bangladesh, Sri Lanka, Burma and Thailand. In Burma it has been the 5th most important cause of death. Its venom is of great interest to laboratory scientists and clinicians. The precoagulant activity of the venom was used by Macfarlane and others to elucidate the human clotting cascade. Up to 70% of the protein content is phospholipase A2, present in the form of at least 7 isoenzymes. Possible clinical effects of the enzyme include haemolysis, rhabdomyolysis, pre-synaptic neurotoxicity, vasodilatation and shock, release of endogenous autacoids and interaction with monoamine receptors. Russell's viper bite is an occupational hazard of rice farmers throughout its geographical range. Defibrination, spontaneous haemorrhage, shock and renal failure develop with frightening rapidity. In several countries, Russell's viper bite is the commonest cause of acute renal failure. There is a fascinating geographical variation in the clinical manifestations, doubtless reflecting differences in venom composition. Conjunctival oedema is unique to Burma, acute pituitary infarction to Burma and south India, and rhabdomyolysis and neurotoxicity to Sri Lanka and south India. Treatment with potent specific antivenom rapidly controls bleeding and clotting disorders, but may not reverse nephrotoxicity and shock. Causes of death include shock, pituitary and intracranial haemorrhage, massive gastrointestinal haemorrhage and acute tubular necrosis or bilateral renal cortical necrosis. The paddy farmer and the Russell's viper coexist in fragile symbiosis. The snake controls rodent pests but inevitably interacts with man, often with mutually disastrous results.

Acute Kidney Injury↗
PubMed1991

Local edema induced by the black-bellied hornet (Vespa basalis) venom and its components.

The black-bellied hornet, Vespa basalis, is one of the most dangerous species of wasp in Taiwan. The hornet venom possesses a potent edema-inducing activity in addition to its lethal cardiovascular effect. Rat hind-paw edema induced by the venom was inhibited significantly by antiserotonin compounds (cyproheptadine and methysergide) but not by antihistaminics (chlorpheniramine and diphenhydramine), betamethasone, cromolyn, indomethacin plus nordihydroguaiaretic acid, cellulose sulfate, aprotinin or captopril. However, chlorpheniramine or betamethasone, when given in combination with cyproheptadine, showed a significant further inhibition of the venom-induced edema. Pretreating the rat with compound 48/80 reduced the edematous response to the venom. Four venom components, i.e. the lethal protein, mastoparan B, fraction 3 (containing protease) and fraction 15 (containing serotonin) were involved in the edematous effect of the venom. Paw edema induced by the crude venom and its protein components (lethal protein, mastoparan B and fraction 3) was similar in their responses to antiserotonin compounds and antihistamine (inhibited by cyproheptadine and methysergide but not by chlorpheniramine), while that induced by fraction 15 was inhibited by both. It is postulated that upon hornet stings, fraction 15 is acting as an exogenous serotonin, while the protein components, especially the lethal protein, are responsible for the release of endogenous autacoids in which serotonin plays the most important role in inducing local edema.

Animals↗
PubMed1987

Effect of platelet-activating factor (PAF-acether) and its specific receptor antagonist, BN 52021, on interleukin 1 (IL1) release and synthesis by rat spleen adherent monocytes.

PAF-acether, at doses ranging from 1pM to 0.1 microM did not induce a significative release and/or synthesis of IL1 from monocytes. In contrast, depending upon the dose of the mediator, adverse effects on the lipopolysaccharide (LPS)-induced IL1 release and synthesis were observed. PAF-acether at 1pM increased IL1 release by 120 +/- 39% and synthesis by 87 +/- 27% whereas at 0.1 microM a decrease of IL1 release of 52 +/- 9% and synthesis of 46 +/- 6% were observed. BN 52021, a specific PAF-acether receptor antagonist, reversed by more than 70% the increase of inhibition of LPS-induced IL1 release and synthesis induced by 1pM and 0.1 microM of the autacoid, respectively. No direct effect of BN 52021 on IL1 release and synthesis from adherent monocytes was noted. These results indicate that PAF-acether modulates monocytes functions, possibly via specific binding sites.

Animals↗
PubMed1988

Effects of anti-asthma drugs on PAF-induced death in mice.

A number of anti-asthma drugs was assayed for the ability to protect mice from platelet-activating factor (PAF)-induced death, which has been suggested to be dependent on the bronchoconstrictive features of this autacoid. Salbutamol, dexamethasone, theophylline, ketotifen and zindotrine, administered parenterally, produced a dose-dependent protection, while forskolin, enprofylline, disodium cromoglycate, nedocromil, azelastine and antagonists of acetylcholine, histamine and serotonin were devoid of protective effects. Theophylline, contrary to salbutamol, lost its protective effects in adrenalectomized mice, suggesting that these effects are dependent on the release of adrenomedullary cathecolamines. Salbutamol, theophylline and dexamethasone, at doses capable of inhibiting PAF-induced death, did not affect PAF-induced haemoconcentration in mice, thus excluding widespread changes in vascular permeability as a major cause of death. These results are generally in agreement with the hypothesis that airway obstruction is an important determinant of PAF-induced death in mice.

Adrenalectomy↗
PubMed1990

Endogenous prostaglandins: its role in gastric mucosal blood flow and ethanol ulceration in rats.

The involvement of endogenous prostaglandins (PGs) in modulating gastric mucosal blood flow (GMBF) is still unclear. The present study was designed to demonstrate the role of this autacoid in the basal GMBF and the restoration of blood flow after restriction of blood supply to the stomach. The ex-vivo gastric chamber was prepared and the GMBF was measured by a laser Doppler technique. 20% ethanol incubation for 10 min in the chamber increased the basal GMBF and lessened the reduction of blood flow induced by absolute ethanol. It also decreased lesion formation caused by ethanol. Indomethacin 5 mg/kg, given s.c 60 min before experimentation had the opposite effects. Ligation of the gastric artery for 20 min which reduced the GMBF by 60%, worsened ethanol ulceration. There was a marked rebound of the GMBF after the ligation was released. Indomethacin totally abolished the blood flow rebound and aggravated ethanol ulceration. However, 20% ethanol incubation significantly potentiated such a rebound in blood flow and reduced lesion formation. Indomethacin pretreatment reversed these actions, whereas misoprostol administration produced the similar effects as 20% ethanol. It is concluded that GMBF plays an important role in ethanol ulceration and both basal and rebound GMBF is probably modulated by endogenous PGs.

Alprostadil↗
PubMed1994

The production of experimental cholecystitis by endotoxin.

Acute acalculous cholecystitis (AAC) is a severe inflammatory disorder of the gallbladder. It occurs primarily in patients acutely ill from other disorders and is related to sepsis and shock. We previously found that platelet-activating factor (PAF), a phospholipid autacoid purported to be a mediator of the shock response, produced AAC. This study was performed to determine the effect of intravenous lipopolysaccharide (LPS) on feline gallbladders. Anesthetized cats underwent LPS administration with and without administration of a cyclooxygenase inhibitor and PAF antagonist. Gallbladder inflammation was evaluated by quantitation of luminal water transport and tissue myeloperoxidase levels. In an attempt to understand the mechanisms of the response, gallbladder perfusate and tissue prostanoid and PAF levels were quantitated as were serum PAF levels. LPS administration resulted in alteration of the normal absorptive pattern of the gallbladder mucosa to exsorption of fluid into the gallbladder lumen, increased tissue myeloperoxidase levels and increased serum PAF levels. This was associated with increased gallbladder tissue and perfusate prostanoid levels and increased perfusate PAF levels. Indomethacin prevented the pro-inflammatory changes in the gallbladder produced by LPS. The PAF antagonist, alprazolam, increased gallbladder prostanoid production when administered alone and with LPS. The administration of LPS resulted in the production of acute changes in the gallbladder consistent with cholecystitis. These changes being prevented by a cyclooxygenase inhibitor suggests that development of AAC may be related to the release of systemic and local pro-inflammatory substances.

Alprazolam↗
PubMed1986

A strain-gauge myograph for isometric measurements of tension in isolated small blood vessels and other muscle preparations.

Isometric tension measurements in vitro on small vessels are important in studies of pharmacodynamic vascular effects of drugs and autacoids. The present study describes a precision myograph equipped with a newly constructed highly isometric strain-gauge transducer used in conjunction with a very sensitive, low-noise and virtually drift-free dc-amplifier. The isometric quotient of the transducer, defined as deflection in micrometer per g of force, is about 5.2. The transducer resonance frequency is 341 c/sec with a damping constant of 1.05. The highest sensitivity of the transducer in connection with the matching dc-amplifier is about 170 mV/V/g force. The practical working range of the myograph is from 2 mg to about 10 g of applied tensile force. Tubular segments of vessels with internal diameters down to 150 micron can be mounted in the myograph on two stainless-steel pins submerged in a 5 ml preparation bath. Precise mounting and setting of passive (resting) tension is assured by the use of micrometer-equipped adjustable miniature mounting tables suspended by roller bearings. The myograph may be provided with electrodes for field-effect stimulation of the vessel preparations. Other muscle preparations may also be mounted in the myograph. Application of the myograph in studies on rabbit coronary arteries is demonstrated by a length-tension diagram obtained in experiments with tubular segments (inner diameter about 500 micron) of the circumflex branch on the left coronary artery, which shows a typical course in development of active and passive tension of the smooth musculature when exposed to alternating potassium depolarization and increasing mechanical stretching. The potassium contracture of the coronary vessels and the log-concentration/response relationship at accumulating potassium concentrations were also investigated.

Animals↗