Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00790 (PGA)
 2,475 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Treatment of mammalian plasmas with pepsin yielded extraordinary quantities of immunoreactive neurotensin (iNT) and methionine5-enkephalin (iENK). The concentrations measured after pepsin-treatment (iNT, 1-5 microM and iENK, 0.1-0.5 microM) were 1-100 thousand times the normal circulating levels of these peptides. The reactions were shown to be time, temperature and pH dependent and to involve the action of pepsin on albumin-like proteins (Mr, ca, 65,000). Pepsin-generated iNT from rat plasma differed from NT since it reacted only with C-terminal directed antisera and eluted earlier than NT during HPLC on mu-Bondapak C-18. Partially purified iNT was active in two bioassays for NT, one which senses changes in vascular permeability to protein after intradermal injection into rats and another which measures release of histamine from isolated rat mast cells. Other biologic activities generated by pepsin-treating plasma included effects on systemic blood pressure in rats and on the contractility of the isolated guinea pig ileum. Some of these, however, were attributable to the formation of angiotensin- and bradykinin-related peptides. Pepsin-generated iENK gave three major peaks during HPLC, one of which (ca, 25%) co-eluted with oxidized ENK and also registered in a radioreceptor assay for opiate-related substances. In addition, this material produced ENK-like effects on the isolated guinea pig ileum and on vascular permeability in rat skin. The precursor-like protein(s) for iENK were distinguished from adrenal proenkephalins since it did not liberate iENK upon digestion with trypsin and carboxypeptidase B. Since pepsin can mimic renin these results suggest the existence of systems in blood (analogous to the renin/angiotensin system) for the generation of biologically active NT- and ENK-related peptides and they also raise the question as to whether other neuropeptides might be found circulating in precursor form(s).
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PMID:Generation of immunoreactive neurotensin(s) and enkephalin(s) by pepsin-treatment of plasma. 310 14

The histamine H2-receptor antagonist cimetidine (25-100 mg/kg) caused a partial inhibition of the pronounced blood pressure fall induced by dextran (Macrodex, 40-100 mg/kg) in the rat. The inhibition by cimetidine could not be distinguished from the inhibition achieved by the serotonin D-receptor antagonist bromolysergic acid diethylamide (BOL, 1-4 mg/kg). Doses of cimetidine and BOL that gave submaximum inhibitory effects separately, showed approximately additive effects when combined. The combined effect of these drugs never exceeded the maximum effects of the drugs separately, whereas injection of tranexamic acid (AMCHA, 100-300 mg/kg) together with cimetidine or BOL, increased the total inhibition. Previous works showed that dextran injected intravenously into rats reduced the level of plasminogen (PG) and plasminogen proactivator (pro-PGA) in plasma (Briseid et al. 1979; Berstad 1980a; Berstad & Briseid 1982). High doses of AMCHA (200 mg/kg) did not inhibit these effects, but significantly increased the lowering caused by dextran of the capacity of high molecular weight kininogen (HMWK) to function as a cofactor in the activation of factor XII. BOL (1-4 mg/kg, Berstad 1981) and cimetidine (50-100 mg/kg) also reduced the cofactor capacity of HMWK in the doses that were required to provide a manifest inhibition of the dextran-induced blood pressure fall. It is suggested that the early phase of the state of shock induced by dextran in the rat can be counteracted at different sites, correlated with histamine and serotonin receptors on the one hand, and with an effect antagonized by AMCHA, on the other. The lowest effective doses of cimetidine and BOL were rather high, suggesting a less specific mechanism for their effects than inhibition at selective receptor sites.
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PMID:The initial phase of the dextran-induced anaphylactoid reaction in the rat: a comparison of inhibitors of the blood pressure fall. 618 May 99

The intravenous injection into rats of dextran with a molecular weight of 1,000 (LMr dextran) in doses greater than or equal to 200 mg/kg induced rapid, but transient falls in blood pressure. Pretreatment of the rats with LMr dextran 200 mg/kg caused a partial inhibition of the profound blood pressure fall induced by the injection of clinical dextran with a molecular weight of 70,000 (HMr dextran), 40 mg/kg. In accordance with previous works (Briseid & Berstad 1981; Berstad & Briseid 1982; Berstad 1982) it was found that the intravenous injection of HMr dextran lowered the plasma levels of plasminogen proactivator (pro-PGA) and functionally active high molecular weight kininogen (HMrK). Also LMr dextran, 200 mg/kg, induced significant reductions in the mentioned parameters, but less extensive than those obtained by HMr dextran, 40 mg/kg, and pretreatment of the rats with LMr dextran inhibited the subsequent effects of HMr dextran. It is suggested that a dextran-activated plasminogen activator might be an early link in the mechanism underlying the dextran-induced state of shock in the rat.
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PMID:Inhibition by low molecular weight dextran of the blood pressure fall and the lowering of plasminogen proactivator induced by clinical dextran in the rat. 618 62

In 15 anesthetized rabbits the reflex changes in arterial pressure, heart rate and respiratory rate in response to injections of bradykinin inorganic phosphate and prostaglandins into femoral artery have been studied. Intraarterial injection of bradykinin produced a reflex fall in arterial pressure, bradycardia and tachypnea. The latency of response ranged from 6 to 7 sec. The threshold dose was about 50 ng. This effect was accompanied by a consistent increase in the afferent discharge in the saphenus nerve. Isotonic mixtures of Na2HPO4 and NaH2PO4 at pH 7, PGE1, PGE2, and PGA, when injected into femoral artery even in high doses, failed to produce any significant cardiocirculatory or respiratory reflex responses. Infusion of PGE1 (1 ug/min) into femoral artery, although inactive by itself, enhanced the reflex effect of bradykinin.
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PMID:[Comparative study of cardiocirculatory response and respiratory reflex to the injection of bradykinin, inorganic phosphates and prostaglandins into the femoral artery]. 730 10