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At least 703 records · Page 39Linked to original sources
PubMed1988

[Histamine and lung cancer. II. Human lung cancer cell line and histamine].

Using tissue culture and biochemical technique, the effects of autacoid-histamine and histamine H-2 receptor's antagonist-cimetidine on human lung cancer cell line were studied. It was shown that histamine at the concentration of 1.8 x 10(-7) M stimulated proliferation of the lung cancer cells, but histamine at the concentration of 1.8 x 10(-4) M or cimetidine at 1.76 x 10(-7) M inhibited growth of the lung cancer cells. Relation between histamine, histidine decarboxylase, histamine formation capacity and tumor proliferation is discussed.

Adenocarcinoma↗
PubMed1987

Effects of histamine on the metabolism of isolated rat hepatocytes: roles of H1- and H2-histamine receptors.

In isolated rat hepatocytes histamine stimulates in a dose-dependent fashion three of the major metabolic pathways: glycogenolysis (70-80% increase over basal), gluconeogenesis from lactate (50-60%), and ureagenesis (50-60%). It was observed that both H1 and H2 receptors mediate the action of histamine and that, in control hepatocytes, the H1-mediated action predominates over the H2. The H1-mediated effect diminished in the absence of extracellular calcium, whereas the H2-mediated action did not. Interestingly, in hepatocytes from hypothyroid rats, the H2 action increased and the H1-mediated effect decreased as compared to those in the controls, with an inversion in efficacy (i.e., H1 greater than H2 in the controls and H2 greater than H1 in cells from hypothyroid rats). Furthermore, it was observed that pertussis toxin treatment and forskolin both enhance the H2-mediated effects without altering the H1-mediated actions of histamine (i.e., H1 approximately equal to H2). The active phorbol ester, phorbol 12-myristate 13-acetate, did not alter the effect of the autacoid. In summary, the data show that histamine modulates liver metabolism through H1 and H2 receptors. The relative importance of the two receptor types in mediating the actions of histamine varies depending on the specific conditions used.

Animals↗
PubMed1987

Consequences of activation and adenosine-mediated inhibition of granulocytes during myocardial ischemia.

During acute myocardial ischemia, granulocytes accumulate and obstruct the microcirculation. Granulocytes remain plugged in individual myocardial capillaries on reperfusion and are the major cause of the no-reflow phenomenon. During 3 h of ischemia, the granulocyte content of myocardium measured by 111In labeling increases from 1.0 X 10(6) to 1.5 X 10(6) cells/g, and after 5 min of reperfusion increases to 2.4 X 10(6) cells/g. The effects of granulocytes during 1 h of acute ischemia were determined by comparing agranulocytic to whole blood perfusion. With whole blood collateral flow decreased, water content increased (edema), ventricular fibrillation was common, and 27% of capillaries had no-reflow, whereas in the absence of granulocytes, collateral flow increased, there was no edema, arrhythmias were rare, and the no-reflow phenomenon was completely prevented. It is unfortunate that the inflammatory signals triggered by ischemia remain active on acute reperfusion, limit tissue salvage, and perhaps cause reperfusion injury. Several activating stimuli for granulocytes are known, but what inhibits them? Adenosine is known to inhibit superoxide radical formation by granulocytes, and 5-amino-4-imidazole carboxamide-riboside (AICA-riboside) augments adenosine release from energy-deprived cells. In dogs subjected to 1 h of ischemia, AICA-riboside pretreatment augmented adenosine release by nearly 10-fold, which was accompanied by a significant increase in collateral blood flow and decreased arrhythmias. We propose a new hypothesis: adenosine acts as a natural antiinflammatory autacoid during transient injury linking the ability to catabolize ATP (an indicator of viability) to granulocyte inhibition, thus preventing premature activation of the inflammatory response to cell death. Granulocytes are active participants in acute myocardial ischemia and means to prevent their activation, remove them from the reperfusate, or inhibit them will be necessary for optimum reperfusion salvage.

Adenosine↗
PubMed1987

Ontogeny of the responsiveness to intravenous platelet-activating factor.

Neonatal and young animals fail to develop antigen-induced, lethal, systemic anaphylactic reactions. Recent evidence has documented that, in the adult rabbit, an unusual phospholipid autacoid, platelet-activating factor, induces almost all of the physiologic events associated with IgE-induced anaphylaxis. Thus, in the present study, the intravascular alterations after intravenous infusion of synthetic platelet-activating factor (1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine; AGEPC) into young rabbits were examined. In comparison to 13-week-old, adult rabbits, the intravascular infusion of greater than 1.0 micrograms/kg AGEPC was not lethal in rabbits of 8 weeks of age or less. In dose-response studies, the amount of AGEPC required to induce a lethal response in 50% of the animals tested (LD50) was found to inversely correlate with age. In contrast, AGEPC-induced platelet aggregation in vitro was not affected by the age of the donor animal. Consistent with age-independent platelet responsiveness in vitro, AGEPC-induced thrombocytopenia and intravascular accumulation of platelet factor 4 and thromboxane B2 were also unaffected by animal age. Neutropenia and basopenia, as well as platelet and neutrophil sequestration in the pulmonary microvasculature after intravenous AGEPC infusion also were similarly unaffected by animal age. Although the mechanisms which modulate the profound and lethal physiologic responses following AGEPC infusion in the adult rabbit remain to be established, the current study clearly documents an age-dependent acquisition of systemic physiologic sensitivity to AGEPC and/or other mediators released as a result of intravascular AGEPC administration.

Aging↗
PubMed1986

Inhibition of collagen-induced platelet activation by 5'-p-fluorosulfonylbenzoyl adenosine: evidence for an adenosine diphosphate requirement and synergistic influence of prostaglandin endoperoxides.

The relative roles of platelet autacoids such as adenosine diphosphate (ADP), prostaglandin endoperoxides, and thromboxane A2 (TXA2) in collagen-induced platelet activation are not fully understood. We reexamined this relationship using the ADP affinity analogue, 5'-p-fluorosulfonylbenzoyl adenosine (FSBA), which covalently modifies a receptor for ADP on the platelet surface, thereby inhibiting ADP-induced platelet activation. Collagen-induced shape change, aggregation, and fibrinogen binding were each fully inhibited under conditions in which FSBA is covalently incorporated and could not be overcome by raising the collagen used to supramaximal concentrations. In contrast, TXA2 synthesis stimulated by collagen under conditions that produced maximum aggregation was only minimally inhibited by FSBA. Since covalent incorporation of FSBA has been previously shown to specifically inhibit ADP-induced activation of platelets, the present study supports the contention that ADP is required for collagen-induced platelet activation. Under similar conditions, indomethacin, an inhibitor of cyclooxygenase, inhibited collagen-induced shape change, indicating that endoperoxides and/or TXA2 also play a role in this response. Shape change induced by low concentrations (10 nmol/L) of the stable prostaglandin endoperoxide, azo-PGH2, was also inhibited by FSBA. These observations indicate a role for ADP in responses elicited by low concentrations of endoperoxides. However, at higher concentrations of azo-PGH2 (100 nmol/L), inhibition by FSBA could be overcome. Thus, the effect of collagen apparently has an absolute requirement for ADP for aggregation and fibrinogen binding and for both ADP and prostaglandins for shape change. Aggregation and fibrinogen binding induced by prostaglandin endoperoxides also required ADP as a mediator, but ADP is not absolutely required at high endoperoxide concentration to induce shape change.

Adenosine↗
PubMed1985

Opioids and neuropeptides: mechanisms in circulatory shock.

Endogenous opioid systems are activated in stressful situations such as circulatory shock. The opiate antagonist naloxone improves cardiovascular function in several models of shock caused by endotoxemia, hypovolemia, anaphylaxis, and spinal trauma. The ergotropic neuropeptide, thyrotropin-releasing hormone, in supraphysiological doses, also improves cardiovascular function in these shock models, but this effect does not result from action at the opiate receptor. For both these agents a central nervous system (CNS) site of action has been partially characterized. A variety of neuropeptides, including the opioids, seem capable of modulating autonomic function through their CNS actions. In addition, they may play a role in peripheral integration and transmission of autonomic nervous activity by actions at the ganglia and/or at nerve endings. Some neuropeptides also have direct autacoid effects on cells, including those of the microvasculature. This raises new questions concerning possible peripheral functions of neuropeptides during circulatory shock, and the nature of their interactions with other potential shock mediators such as monokines and arachidonic acid derivatives.

Adrenal Glands↗
PubMed1985

[Metabolic pathways of arachidonic acid: prostaglandins, thromboxane and leukotrienes].

The powerful and varied biological effects of the metabolites of arachidonic acid suggest that they may play a role in cardiovascular diseases. These substances seem to be involved in a number of pathological situations although there are few satisfactory methods of assessing their role in vivo. At present, it is very difficult to elaborate experiments and/or tests to analyse the production of these autacoids in protocols of clinical investigation reflecting a pharmacological or pathological condition. The development of new methods of study should provide information about the role of these metabolites in the development of cardiovascular diseases.

Arachidonic Acids↗
PubMed1979

Pharmacological reactions of the circular muscle of the guinea pig vas deferens.

Pharmacological responses of spiral strips prepared from the guinea pig vas deferens to various adrenergic and cholinergic agonists and autacoids were studied. On the circular muscle alpha adrenergic, muscarinic cholinergic and histaminergic receptors were identified. The responses evoked on the circular and longitudinal muscles were of the same type.

Adrenergic Agonists↗
PubMed1982

Pharmacological modification of the edema produced by combined infusions of prostaglandin E1 and bradykinin in canine forelimbs.

In dogs anesthetized with pentobarbital, 60 min local i.a. infusions of prostaglandin E1 (4 micrograms/min) together with bradykinin (10 micrograms base/min) into forelimbs perfused at a constant pump controlled flow rate produced decreases in perfusion pressure and very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight (266 g). Pretreatment with indomethacin did not significantly reduce the very marked increases in these parameters produced by the combined prostaglandin E1-bradykinin infusions. Treatment with diphenhydramine completely prevented the increases in lymph flow, lymph total protein concentration, total protein transport, weight and vasodilation produced by infusions of histamine, but not those produced by infusions of prostaglandin E1 or bradykinin. Pretreatment with methylprednisolone prevented the increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by infusions of prostaglandin E1, but not those produced by infusions of high doses of histamine or bradykinin. Treatment with either methylprednisolone or diphenhydramine significantly reduced the very marked increases in these parameters produced by combined infusions of prostaglandin E1 and bradykinin to levels produced by infusions of bradykinin alone. Vasopressin or isoproterenol treatment essentially prevented the very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by combined infusions of prostaglandin E1 and bradykinin. These data suggest that the potentiation of the bradykinin edema formation produced by prostaglandin E1 results from an endogenous release of histamine and that treatment with vasopressin or isoproterenol essentially prevents the development of edema produced by combined infusions of these autacoids. Moreover, the potentiation is not dependent on the vasodilator action of prostaglandin E1 as it may be demonstrated under constant controlled flow conditions.

Alprostadil↗
PubMed1984

[Polypeptides and antagonists].

Polypeptides are endogenous agents, involved in the regulation of many physiologic functions and the pathogenesis of several diseases. Polypeptide antagonists form a group of new chemical entities which may provide valid therapeutic agents. Some polypeptides (angiotensin, kinins) are released through the action of proteolytic enzymes (renin, kallikreins) and act as hormones or autacoids; others (substance P, neurotensin) are synthetized by nervous cells to serve as neurotransmitters or neuromodulators. The main homeostatic role of the renin-angiotensin system is to uphold high systemic arterial blood pressure. Overproduction of renin and insufficient checking of renin secretion are among the most common causes of arterial hypertension. Several forms of arterial hypertension (neurovascular, idiopathic) benefit from a reduction in renin-angiotensin system activity. This is achieved either through decreasing renin secretion, by inhibiting conversion of angiotensin I into angiotensin II, or through blocking the peripheral actions (at the receptor sites) of angiotensin II. Renin secretion is very significantly reduced by beta-blocking agents (propranolol); conversion of angiotensin I into angiotensin II is inhibited by teprotide, captopril and their derivatives; peripheral actions of angiotensin II are blocked by saralasin. Bradykinin and related agents produce vasodilation, increase vascular permeability and stimulate pain fibers. Kinins thus reproduce the cardinal features of inflammation and are held to be mediators of the inflammatory reaction. The substance P neuropeptide is found in the brain and bowel; it may act as a transmitter of the sensation of pain at the spinal cord and central nervous system sites. Among other effects outside of the brain, substance P is a potent vasodilator and inhibits renin secretion. Neurotensin is a neuropeptide which produces hypothermia, muscular relaxation and analgesia. Outside of the brain, this peptide is involved in the regulation of gastric secretion, intestinal motility and insulin and glucagon secretion. The vasoactive intestinal peptide, found in certain cholinergic nerve endings, is a large peptide which inhibits gastric secretion, intestinal motility and vascular tone.

Angiotensin II↗
PubMed1984

[Prostaglandins, thromboxanes and leukotrienes. Their role in cardiovascular diseases, allergic reactions and inflammation].

Prostaglandins, thromboxanes and leukotrienes are oxygen metabolites of arachidonic acid forming a family of lipidic substances with intrinsic biological activities. The significance of biosynthesis of these mediators in response to cell stimulation remains unclear. Numerous data suggest that these compounds, produced by blood cells and vascular cells, play an important role in cardiovascular pathology, allergy or inflammation. The concept, based on biochemistry, of distinct metabolic pathways should be reappraised, using a physiological approach that involves a biological effect resulting from a synergistic action of different compounds. The development of specific assay methods will permit to investigate compounds obtained from biological fluids or from cells present in recognized pathological situations. Such in vitro data should help to clarify the role of these autacoids in cardiovascular, allergic or inflammatory diseases.

Animals↗
PubMed1983

Nicotinic acid action on gastrointestinal smooth muscle.

The mechanism of nicotinic acid action in smooth muscle was studied by testing the drug in rat stomach fundus and descending colon using either the superfusion or perfusion technique. In the rat stomach strips nicotinic acid (or Na-nicotinate) induces concentration-dependent contractions that are drastically antagonized by indomethacin but not by the other inhibitors tested (scopolamine, phenoxybenzamine, propranolol, methysergide, pyrilamine, imidazole, anacardic acid). Reduced glutathione, on the contrary, clearly potentiates the contractile effect of nicotinic acid in the tissue. The response of the rat stomach strips to different prostanoids (PGE1, PGE2 alpha, PGF2 alpha, and PGI2) shows that only PGE2 (at a very low concentration: 14 nM) induces muscle contraction similar to that evoked by Na-nicotinate (34.4 nM). In segments of rat descending colon Na-nicotinate induces concentration-dependent contractions that are abolished by scopolamine, by hemicholinium-3 or incubation at low temperature (20 degrees C). These results provide evidence that nicotinic acid influences gastrointestinal smooth muscle by indirect mechanisms, i.e. by release of endogenous autacoids, namely prostaglandins in the stomach fundus and cholinergic transmitter in the descending colon.

Animals↗
PubMed1983

Contractile activity of the isolated rat vas deferens and release of prostaglandin E and F-like substances. Influences of acetylcholine and inhibitors of cyclo-oxygenase and phospholipase A2.

The isolated epididymal portion of the rat vas deferens releases spontaneously and in response to acetylcholine prostaglandin-like material into the suspending solution. The output of prostaglandin E2 and F2 alpha-like substances, evoked by the cholinergic agonist, was significantly higher than the basal generation. Atropine, but not hexamethonium, markedly reduced the release elicited by acetylcholine. In addition corticosterone, quinacrine and verapamil also decreased significantly the acetylcholine-induced prostaglandin output. Inasmuch as quinacrine and corticosterone antagonized the response to acetylcholine the possible involvement of the cholinergic agonist on the activity of phospholipase A2, is suggested. Furthermore, the role of prostaglandins in relation to the action of acetylcholine on the contractile activity of the epididymal portion of isolated vas deferens, was also explored. It is concluded that these autacoids modulate the contractions evoked by acetylcholine.

Acetylcholine↗
PubMedDate not supplied

Pathogenesis of rheumatoid arthritis.

Rheumatoid arthritis (RA) is initiated by an unknown antigen(s) in the genetically programmed host. HLA-DR4 is associated with RA. The antigen could be exogenous (e.g., Epstein-Barr virus, bacterial cell wall products) or endogenous (e.g., collagen or immunoglobulin). Within the synovium, where the immune response begins, monocytes and lymphocytes are activated. Polyclonal B-cell proliferation results, as well as production of monokines and lymphokines. The antibodies form immune complexes with other antibody molecules or antigens. Phagocytosis of immune complexes results in production of many autacoids and activation of other soluble mediator systems, e.g., the coagulation, kinin, complement, and fibrinolytic systems in synovial fluid. Chemotactic factors draw polymorphonuclear leukocytes into the joint space. Monokines stimulate synovial cell proliferation; these cells, in turn, synthesize proteinases and products of arachidonate metabolism capable of destroying normal articular structures.

Antibodies, Antinuclear↗
PubMed1983

Prostaglandin production by human trabecular cells: in vitro inhibition by dexamethasone.

In addition to the well-known ability of prostaglandins (PGs) to raise intraocular pressure (IOP), it recently has been reported that moderate and low doses of PGE2 and PGF2 alpha significantly reduce IOP in a variety of experimental animals. These studies suggested to us that PGs might serve as endogenous regulators of outflow facility in the meshwork if these autacoids were produced and secreted by human trabecular cells. To examine this possibility, media from well-defined trabecular cell material were assayed using specific radioimmunoassays. Morphologically differentiated human trabecular cells produced high levels of PGE2, and somewhat lower levels of PGF2 alpha and 6KF1 alpha in the presence and absence of serum. In a typical experiment, the following PG levels were detected in the cell culture media after 24 hours: PGE2; 225; PGF2 alpha, 33.5; 6KF1 alpha, 12.7 ng/ml with the presence of 10% fetal calf serum; and PGE2, 30.0; PGF2 alpha, 4.8; 6KF1 alpha, 3.6 ng/ml in serum-free media. Since glucocorticoids are known to inhibit PG pathways in other tissues, this effect was examined in the cultured trabecular cells. Moderate concentrations of dexamethasone (DEX) produced a marked inhibition in the levels of all three PGs. For PGE2 production, 10(-8) M DEX inhibited approximately 75%, and 10(-7) M DEX inhibited approximately 90%. More detailed dose-response studies revealed that the I50 for inhibition of PG production by dexamethasone was less than 10 nM, thus indicating that the steroid effect probably involved high affinity glucocorticoid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗
PubMed1982

Physiological regulation of the hepatic circulation.

Liver blood flow is determined at normal arterial pressure by 1) the hepatic arterial vascular resistance, 2) the inflow resistance to the preportal vascular beds, 3) the intrahepatic portal venous vascular resistance. Hepatic arterial vascular resistance and therefore blood flow are regulated by relatively weak intrinsic as well as by extrinsic mechanisms. The principal extrinsic mechanisms include the sympathetic vasoconstrictor innervation and epinephrine, whereas the roles of the vasodilator gastrointestinal and pancreatic hormones, and autacoids released from the gastrointestinal tract, remain to be established convincingly. Intrahepatic portal vascular resistance is not significantly controlled by intrinsic mechanisms, and responses to extrinsic mechanisms may be directed principally toward maintenance of portal venous pressure. Two aspects of liver blood flow are discussed in particular detail. First, hormones or drug introduced into one inflow to the liver (e.g., the portal vein) alter the vascular resistance not only of that circuit, but also of the other inflow circuit (hepatic arterial) by a transhepatic mechanism that does not depend on recirculation of the hormone or drug. Second, glucagon, but not other polypeptide vasodilator hormones, prevents hepatic arterial vasoconstriction due to stimuli that include sympathetic nerve activation. This effect occurs at portal or arterial glucagon concentrations close to the pathophysiological range.

Animals↗
PubMed1982

The role of the arachidonic acid cascade in the species-specific X-ray-induced inflammation of the rabbit eye.

To identify the mediator(s) of the apparently species-specific X-ray-induced inflammation of the rabbit eye, inhibitors of the synthesis and/or release of known or putative mediators of ocular inflammation were administered prior to irradiation. The X-ray-induced ocular inflammation, particularly the rise in intraocular pressure, was found to be inhibited by intravenous pretreatment of rabbits with flurbiprofen, indomethacin, or imidazole (1, 10, and 100 mg/kg i.v., respectively), or by combined intravitreal and topical administration of flurbiprofen. Systemic, intravitreal, and/or topical pretreatment with prednisolone or disodium cromoglycate or the retrobulbar injection of ethyl alcohol or capsaicin failed to block the inflammatory response, whereas vitamin E apparently exerted some protective effect. These findings show that the X-ray-induced inflammation of the rabbit eye is mediated, at least in part, by prostaglandins (PGs) and/or related autacoids. In addition, these results suggest that the unique sensitivity of the rabbit eye to X-ray-induced inflammation is due either to the presence in this species of a unique or uniquely effective triggering mechanism for the release of PG precursors or to the greater sensitivity of this species to the ocular inflammatory effects of PGs. Thus the rabbit eye may provide a unique model for studying some aspects of arachidonic acid release or ocular PG effects, but extreme caution must be exercised in generalizing such findings to other species.

Animals↗
PubMed1982

Influence of corticoids on the production of glomerulopressin by isolated rat liver.

The isolated liver of rats treated with dexamethasone, hydrocortisone, and deoxycorticosterone acetate (DOCA) was perfused with Krebs-Ringer Bicarbonate (KRB). The liver of adrenalectomized rats was also perfused with KRB. The glomerulopressin activity of the ultrafiltrate of the liver perfusates was assayed in the tonic tension contraction (TTC) of isolated stomach fundus from rats. As glomerulopressin is known to be a glucuronide, it was inactivated with beta-glucuronidase to confirm that the effect on the stomach fundus was due to the glomerulopressin and not to an autacoid. It was observed that dexamethasone, hydrocortisone and DOCA inhibit glomerulopressin production, but adrenalectomy had no effect, therefore it can be deduced that the adrenals are not necessary for the production of glomerulopressin.

Adrenalectomy↗