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At least 235 records · Page 13Linked to original sources

PubMed1991

The effect of ONO-3708, a novel TxA2 receptor antagonist, on U-46619-induced contraction of guinea pig and human tracheal strips in vitro and on bronchoconstriction in guinea pigs in vivo.

The effect of (9, 11), (11, 12)-didedoxa-9 alpha, 11-alpha-dimethylmethano-11,12-methano-13,14-dihydro-13-aza-14-oxo -15-cyclo-pentyl-16, 17, 18, 19, 20-pentanor-15-epi-TxA2 (ONO-3708) on 9,11-methanoepoxy-prostaglandin H2 (U-46619)-induced contraction of airway smooth muscle in the guinea pigs and human in vitro and bronchoconstriction in guinea pigs in vivo was investigated. In in vitro experiments, ONO-3708 inhibited the U-46619-induced contraction of isolated guinea pig and human tracheal smooth muscle in a dose related fashion (guinea pig; pA2=7.78, human; pA2 = 7.43). The contractions of guinea pig tracheal muscle caused by histamine and leukotriene D4 (LTD4) were not inhibited by ONO-3708. In in vivo experiments, intravenous injection of ONO-3708 at doses between 1 and 20 mg/kg inhibited the U-46619-induced increase of airway insufflation pressure as measured by Konzett-Rössler method. In addition, ONO-3708 inhibited the U-46619-induced increase in airway reactivity to acetylcholine. These data suggest that ONO-3708 has possible therapeutic utility for asthma in which TxA2 participates.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1984

The effect of ethylenedinitrilotetraacetic acid (EDTA) on the reaction between the guinea-pig C5 convertase and guinea-pig C5.

Guinea-pig C5 was reacted with EAC1423 in the washed-cell intermediate assay in the presence of glucose gelatin veronal buffer (GGVB), Zn2+-GGVB (0.025 mM), GGVB2+ containing Ca2+ and/or Mg2+ or EDTA (0.013 M)-GGVB. The EDTA inhibited the formation of competent SAC14235, while Ca2+ and/or Mg2+ had a slight enhancing effect compared to GGVB alone and Zn2+ gave a four-fold increase. Similar results were obtained by using human C5 with guinea-pig C5 convertase and functionally pure guinea-pig C6, C7, C8 and C9. When guinea-pig C6 was incorporated into these various reaction mixtures with guinea-pig C5, its addition markedly reduced the inhibition by EDTA, while Zn2+ still showed an enhancing effect. These results demonstrate that EDTA inhibited formation of competent SAC14235 by preventing activation of C5. The association of C6 with C5 can partially overcome the inhibition of C5 conversion by EDTA and may account for C5 activity in reaction mixtures containing C-EDTA.

Animals↗

PubMed1991

Calcitonin gene-related peptide (CGRP) modulates cholinergic neurotransmission in the small intestine of man, pig and guinea-pig via presynaptic CGRP receptors.

The effect of calcitonin gene-related peptide (CGRP) on the cholinergically mediated twitch contraction in longitudinal muscle strips of the small intestine (duodenum, jejunum, ileum) of guinea-pig, pig and man was investigated. Independently of the anatomical region, CGRP inhibited the twitch response in the different specimens of all three species by about 40% with similar IC50 values (1.5-2.4 nmol/l). Only in the guinea-pig small intestine CGRP induced a contraction of the smooth muscle which was sensitive to scopolamine and tetrodotoxin. The electrically evoked [3H]acetylcholine release from jejunal longitudinal muscle strips with myenteric plexus attached of the guinea-pig, which were incubated with [3H]choline, was concentration-dependently inhibited by CGRP. A direct relaxant effect of CGRP on smooth muscle tone of carbachol precontracted preparations was only observed in specimens of the guinea-pig. In conclusion, presynaptic inhibitory CGRP receptors on cholinergic neurones modulate the release of acetylcholine in different parts of the small intestine.

Acetylcholine↗

PubMedDate not supplied

Comparative in vitro effects of guinea pig VIP and common VIP on liver and lung membranes from guinea pig and rat and on human lymphoblastic SUP-T1 membranes.

Guinea pig VIP differs from VIP of several mammals by its amino acids in positions 5, 9, 19 and 26. We tested a) its ability to occupy VIP receptors in liver and lung membranes of rat and guinea pig and in the human lymphoblastic SUP-T1 cell line and b) the ensuing adenylate cyclase stimulation. In liver and lung membranes from rat, guinea pig VIP was less potent than common VIP to occupy high and low affinity VIP receptors. In rat liver both VIP activated adenylate cyclase mostly through high affinity receptors. In rat lung, guinea pig VIP activated the enzyme mostly through high affinity receptors and was less efficient than common VIP acting through both classes of receptors. In guinea pig liver and lung membranes, binding inhibition curves were steeper than with rat preparations and adenylate cyclase appeared to be mostly activated through high affinity VIP receptors in liver and through both classes of receptors in lung. On human lymphoblastic SUP-T1 membranes both VIP were equally potent and efficient to inhibit tracer binding and activate adenylate cyclase.

Adenylyl Cyclases↗

PubMed1984

Effect of thromboxane synthetase inhibitors (OKY-046, OKY-1580) on the action of bronchoactive agents in guinea pig tracheal strips and on arachidonate metabolism in guinea pig lung lobes.

We investigated the effect of the thromboxane synthetase inhibitors, OKY-046 and OKY-1580, on the action of bronchoactive agents in guinea pig tracheal strips, and on arachidonic acid metabolism in isolated perfused guinea pig lung lobes. OKY-046 and OKY-1580 attenuated histamine-, serotonin-, acetylcholine-, bradykinin- and prostaglandin F2- induced contractile responses in guinea pig tracheal strips dose-dependently and potentiated isoproterenol-, salbutamol- and prostaglandin E2-induced relaxation in guinea pig tracheal strips dose-dependently. In addition, OKY-046 and OKY-1580 inhibited the biosynthesis of thromboxane A2 and accelerated the production of 6-keto prostaglandin F1 from arachidonic acid in isolated perfused guinea pig lung lobes. The above results suggest that OKY-046 and OKY-1580 might be useful therapeutic agents for the treatment of pulmonary thromboembolism and chronic obstructive lung diseases.

Animals↗

PubMed1997

Characterisation of excitatory and inhibitory transmitter systems in prostate glands of rats, guinea pigs, rabbits and pigs.

Excitatory and inhibitory transmitter systems were investigated in strips of prostate glands from rats, guinea pigs, pigs and rabbits. In strips from all species, electrical field stimulation (1 ms pulses at 1-30 Hz for 10 s) produced frequency-dependent contractions which were abolished by tetrodotoxin (1 microM). In strips from rats, guinea pigs and rabbits, contractions were reduced by prazosin (1 microM), guanethidine (10 microM) and atropine (2 microM), indicating the presence of noradrenergic and cholinergic mechanisms. However, the smooth muscle in the pig prostate appears to have a non-(nor)adrenergic non-cholinergic (NANC) excitatory innervation for which the transmitter was not identified. When noradrenergic and cholinergic mechanisms were blocked by guanethidine and atropine, respectively, and tone was raised with noradrenaline or methoxamine, field stimulation produced relaxations only in strips of rabbit prostate, and these were greatly reduced by N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM), providing functional evidence for a nitrergic relaxant innervation. In accord with this, nitric oxide (NO) synthase activity was considerably higher in rabbit than in rat or pig prostates.

Animals↗

PubMed1998

[3H]RS79948-197 binding to human, rat, guinea pig and pig alpha2A-, alpha2B- and alpha2C-adrenoceptors. Comparison with MK912, RX821002, rauwolscine and yohimbine.

The Kd values of the recently introduced radioligand [3H]RS79948-197 ((8a R,12aS,13a-S)-5,8,8a,9,10,11,12,12a,13,13a-decahydro-3-metho xy-12-(ethylsulphonyl)-6H-isoquino[2,1-g][1,6]naphthyridine) were determined for the recombinant human and rat alpha2A-, alpha2B- and alpha2C- as well as guinea pig alpha2B- and alpha2c-adrenoceptors expressed in COS (CV-1 Origin, SV40) cells. In addition, the Kd values were also determined for [3H]RS79948-197 for the guinea pig spleen alpha2A-adrenoceptor and for pig alpha2A-, alpha2B- and alpha2C-adrenoceptors in membranes obtained from kidney and striatum. Available radioligands for alpha2-adrenoceptors, besides [3H]RS79948-197 are the tritiated forms of MK912 ((2S,12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octa hydro-2H-benzo[b]furo[2,3-a]quinazoline)-2,4'-pyrimidin-2'-one), RX821002 (2-methoxy-idazoxan), rauwolscine and yohimbine. In the present article the binding constants of all these substances for the alpha2A-, alpha2B- and alpha2C-adrenoceptor subtypes in human, pig, rat and guinea pig are reviewed. In all species tested MK912 was alpha2C-selective, RX821002 showed a minor alpha2A-selectivity, whereas [3H]RS79948-197 was non-selective among the alpha2-adrenoceptor subtypes, showing high affinity for all three subtypes. Rauwolscine and yohimbine showed relatively low affinities for nmost of the alpha2-adrenoceptor subtypes investigated, the exception being rauwolscine having high affinity for the human and porcine alpha2C-adrenoceptors.

Adrenergic Agents↗

PubMed1992

In vitro activities of fleroxacin against clinical isolates of Legionella spp., its pharmacokinetics in guinea pigs, and use to treat guinea pigs with L. pneumophila pneumonia.

The activities of fleroxacin against 22 clinical Legionella isolates were determined by agar and broth microdilution susceptibility testing. The fleroxacin MIC required to inhibit 90% of strains tested on buffered charcoal yeast extract agar medium supplemented with 0.1% alpha-ketoglutarate was 0.64 micrograms/ml and was 0.04 microgram/ml when testing was done with buffered yeast extract broth supplemented with 0.1% alpha-ketoglutarate. Fleroxacin (0.25 microgram/ml) reduced the bacterial counts of two L. pneumophila strains grown in guinea pig alveolar macrophages by 1 log10 CFU/ml, but regrowth occurred over a 3-day period; fleroxacin was significantly more active than erythromycin in this assay. Single-dose (10 mg/kg of body weight given intraperitoneally) pharmacokinetic studies performed in guinea pigs with L. pneumophila pneumonia revealed peak levels in plasma and lungs to be 3.3 micrograms/ml and 3.5 micrograms/g, respectively, at 0.5 h and 0.8 microgram/ml and 0.8 microgram/g, respectively, at 1 h. The half-life of the terminal phase of elimination from plasma and lung was approximately 2 h. All 17 infected guinea pigs treated with fleroxacin (10 mg/kg/day) for 2 days survived for 14 days post-antimicrobial therapy, as did all 16 guinea pigs treated with the same dose of fleroxacin for 5 days. Only 1 of 16 animals treated with saline survived. The animals treated with fleroxacin for 2 days lost more weight and had higher temperatures than those treated with the antibiotic for 5 days. Fleroxacin is effective against L. pneumophila in vitro and in a guinea pig model of Legionnaires' disease. Fleroxacin should be evaluated as a treatment for human Legionnaires' disease.

Animals↗

PubMed1976

Comparison of guinea pig cytomegalovirus and guinea pig herpes-like virus: pathogenesis and persistence in experimentally infected animals.

The pathogenesis of guinea pig cytomegalovirus (GPCMV) and guinea pig herpes-like virus (GPHLV) in guinea pigs was compared. Animals were inoculated with the two viruses by different routes and sacrificed after varying periods of time. GPCMV was consistently isolated from salivary gland 2 weeks postinoculation and thereafter following intraperitoneal or subcutaneous incoulaton. Virus was less frequently found in other tissues including blood, spleen, and kidney. Intranuclear inclusions were seen in tissue sections of salivary gland after inoculation with GPCMV- infected tissue suspension, but were only rarely found after inoculation with tissue culture virus. In GPHLV-infected guinea pigs, consistent latent infection of leukocytes and other tissues was detected by cocultivation techniques. Intranuclear inclusions were not found in the spleen, salivary gland, or other infected tissues after GPHLV infection with either tissue culture virus or infected tissue suspension. Guinea pigs inoculated with GPCMV produced high titers of specific neutralizing antibody to the homologous virus; those inoculated with GPHLV developed long-term viremia accompanied by minimal neutralizing antibody levels to the virus.

Animals↗

PubMed1979

Humoral immunity in the resolution of genital infection in female guinea pigs infected with the agent of guinea pig inclusion conjunctivitis.

Female guinea pigs infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis were selectively immunosuppressed by varying regimens of cyclophosphamide (Cy) treatment. Temporary suppression of both humoral and cell-mediated immunity by daily treatment of Cy (25 mg/kg) for 13 days resulted in a prolonged infection, whereas daily treatment for the duration of the experiment totally prevented the development of humoral and cell-mediated responses and produced an intense and prolonged infection which did not resolve. When humoral immunity alone was suppressed by treatment with Cy (250 and 150 mg/kg) at 9-day intervals, the infection again did not resolve. Treatment with 100 mg of Cy per kg at 9-day intervals resulted in an extended infection which resolved concomitantly with the development of antibody to guinea pig inclusion conjunctivitis. These data indicate that humoral immunity is essential for the recovery of female guinea pigs from guinea pig inclusion conjunctivitis genital infection. A market weight loss was observed which could not be attributed to Cy treatment alone. Edematous and ulcerative changes of the external genitalia were also noted.

Animals↗

PubMed1973

Guinea pig herpes-like virus infection. I. Antibody response and virus persistence in guinea pigs after experimental infection.

Guinea pigs, experimentally infected with guinea pig herpes-like virus produced antibodies which were detectable by indirect hemagglutination (IHA), complement-fixation (CF), and neutralization tests. The IHA test appeared to be a more sensitive method than the CF or neutralization test for determining antibody response in guinea pigs immediately after infection, but the IHA method was not suitable for the detection of antibody in animals receiving small doses of virus. Antibody titers obtained by CF tests were generally higher than those obtained by the neutralization test, and they followed the same time course when individual animals were studied serially. Intracardiac inoculation produced the best antibody response in guinea pigs when compared with other routes of infection. Guinea pigs infected by the intraperitoneal, intranasal, or oral route showed rising antibody titers but the levels were low. Infectious virus was isolated from and persisted in all inoculated animals in the presence of antibody regardless of the route of inoculation. Recovery of infectious virus required cultivation or cocultivation of tissue cells containing virus. The administration of antilymphocyte sera delayed the appearance of IHA antibody but had no effect on antibodies determined by the CF- and neutralization tests.

Animals↗

PubMed2000

Comparison of enterotoxicity between autumn crocus (Colchicum autumnale L.) and colchicine in the guinea pig and mouse : enterotoxicity in the guinea pig differs from that in the mouse.

Autumn crocus poisoning of cattle is characterized by severe diarrhea caused by alkaloid colchicine. Previously, we examined pathologically this poisoning in cattle and reported that enterotoxic lesions were closely associated with apoptosis. To examine enterotoxicity of autumn crocus more precisely, a reproductive study was performed using guinea pigs and mice, and pathological findings associated with autumn crocus poisoning were compared with those of colchicine. Each group of guinea pigs given the bulb of autumn crocus or colchicine exhibited severe diarrhea. Histopathological findings in intoxicated guinea pigs were entirely consistent with those in the autumn crocus-poisoned cattle. In contrast, each group of mice administered with the bulb or colchicine did not develop diarrhea. Our results confirmed that the toxicity of autumn crocus bulb is attributable to the toxicity of ingredient colchicine, and revealed that the guinea pig has high reproducibility of autumn crocus poisoning in cattle and colchicine poisoning in humans. It has been reported that the physiological mechanism of the apoptotic process for eliminating the enterocytes in the mouse and rat differs from that of the guinea pig, monkey, cattle and horse. Taking the observation that the former animals do not develop diarrhea, whereas the latter animals do so in the autumn crocus or colchicine poisoning into consideration, it would seem that the species-difference in enterotoxicity of autumn crocus may be closely associated with the physiological mechanism of eliminating the effete enterocytes.

Animals↗

PubMed1976

Guinea pig histocompatibility antigens. III. Analysis of normal lymphocyte transfer (NLT) reactions among guinea pigs with serologically defined phenotypes (GPL-AB locus and I region).

The normal lymphocyte transfer (NLT) reaction occurring upon intradermal injection of lymphocytes into a normal recipient may be considered as a kind of mixed lymphocyte reaction in vivo. In previous experiments, we have defined serologically a number of guinea pig lymphocyte antigens, controlled either by a GPL-A locus (equivalent of H-2 D locus in mice) or by a so-called I region (equivalent to the I region in mice). The I region also appears to control a number of immune response genes in the guinea pig. Using guinea pig inbred strains (such as 2, 13, OM3, BE), guinea pig families homozygous for their GPL-A antigens and serologically characterized outbreds, it has been possible to show that antigens of the I region probably play a higher role in NLT reactions. No NLT reactions occur among outbred animals of a closed colony which have been bred to homozygozity for their GPL-A antigens and thereby probably possess haplotype homozygozity for their major histocompatibility complex. The NLT reaction among serologically characterized guinea pigs may become a convenient way to detect new specificities and recombinant progeny.

Animals↗

PubMed1987

Intramural nerve-mediated inotropic responses of left atria of rats and guinea pigs: demonstration of alpha adrenergic and nonadrenergic noncholinergic responses in guinea pigs.

The effects of transmural nerve stimulation (TNS) on contractile responses of rat and guinea pig atria were analyzed pharmacologically. Isolated left atria were electrically driven through AgAgCl field electrodes and TNS was performed by brief introduction of defined stimulation patterns through the same electrodes. Step elevations in stimulating voltage induced biphasic inotropic responses in the left atria of both species: an initial negative component which was usually overwhelmed by a subsequent positive one. The transient negative inotropic response was induced by parasympathetic cholinergic nerve excitation, inasmuch as it was abolished by atropine. In the left atrium of the rat, the TNS-induced positive inotropic response was due exclusively to adrenergic nerve excitation through activation of beta-1 adrenoceptors. In contrast, analysis of the time course of responses in guinea pig left atria after nerve stimulation at 10 Hz revealed a positive inotropic response consisting of two phases; rapid and delayed phases were superimposed upon each other. The rapid phase was reduced by atenolol, a beta-1 antagonist, and attenuated further by prazosin, an alpha-1 antagonist. In the presence of both atenolol and prazosin, TNS of guinea pig left atria still induced a positive inotropic response but it had a slow onset and decay. This is termed the delayed phase response. TNS induced a similar delayed inotropic response in atria from surgically sympathectomized or reserpine-pretreated guinea pigs, from which catecholamine-fluorescence nerves and responses to tyramine were absent. These results demonstrate that TNS excitated adrenergic, cholinergic and nonadrenergic noncholinergic nerves in guinea pig left atria.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1984

Use of bacteria and yeasts to identify T lymphocytes in peripheral blood and lymphoid tissues of healthy guinea pigs and guinea pigs fed aflatoxin.

Fifty-four bacterial and 10 yeast isolates were screened to identify strains that were consistently bound by peripheral blood lymphocytes (PBL) of guinea pigs. None of the yeast isolates examined was bound by guinea pig PBL. Of 54 bacterial isolates, 10 were bound by greater than 5% of PBL. Potential lymphocyte markers from these bacteria were chosen for further study. Sodium azide inhibited the binding of bacteria by PBL. Preparations of T lymphocytes indicated that Salmonella schottmuelleri was bound by most T lymphocytes; Yersinia enterocolitica was bound by a subpopulation of T lymphocytes. Patterns of binding of bacteria by lymphocytes from thymus, lymph node, or spleen differed from binding patterns obtained using PBL. Aflatoxin did not affect the total WBC, differential leukocyte count, absolute lymphocyte count, or relative percentage of PCV of guinea pigs given as much as 0.060 mg of aflatoxin B1 equivalents/kg of body weight/day for 3 weeks. Changes in absolute numbers of peripheral blood T lymphocytes were not observed in guinea pigs given aflatoxin when immunofluorescence or bacterial binding was used to identify lymphocyte populations, except that the number of S schottmuelleri-binding lymphocytes (tentatively identified as T lymphocytes) in guinea pigs given the highest dose of aflatoxin (0.060 mg of aflatoxin B1 equivalents/kg/day) was less than the number of T lymphocytes identified by immunofluorescence.

Aflatoxin B1↗

PubMed1993

[The establishment of a monolayer culture system of guinea pig chief cells and an enzyme immunoassay system for guinea pig pepsinogen].

For the purpose of studying pepsinogen secretion from gastric chief cells, we established a monolayer culture system of guinea pig chief cells and an enzyme immunoassay (EIA) system specific for guinea pig pepsinogen. Dispersed chief cells were obtained from gastric mucosa of a guinea pig using collagenase, GEDTA, and Percoll solution, suspended in DMEM/F-12 (1/1 containing 10% FCS) media, and cultured for 70hr. Then the monolayer culture system was established. Pepsinogen was purified from gastric mucosa of a guinea pig using DEAE-Sephacel and Sephacryl S-200 columns. Antibody to pepsinogen was raised by immunizing rabbit with the purified pepsinogen. A two-site EIA system was then established using beta-galactosidase-labeled Fab' antibody. The EIA system showed sensitivity to measure above 1.5ng of guinea pig pepsinogen, and the monolayer culture system responded well to secretagogues. These systems are useful for studying pepsinogen secretion.

Animals↗

PubMed1997

Antagonistic effects of FR 173657 on human, pig, rabbit, and guinea pig kinin receptors: an in vitro study.

The pharmacodynamic features of the new nonpeptide kinin B2 receptor antagonist FR 173657 were evaluated on pig, rabbit, guinea pig, and human native kinin B2 receptors. FR 173657 exerted high antagonistic activity in all preparations examined. In particular, it acts as a competitive antagonist in the rabbit jugular vein (pA2 8.9) and in the human umbilical vein (pA2 8.2) but as a noncompetitive antagonist in the pig coronary artery (pKB 9.2) and in the guinea pig ileum (pKB 9.2) stimulated with the selective B2 receptor agonist bradykinin (BK). In contrast, FR 173657 failed to antagonize the biological effects of the selective B1 receptor agonist LysdesArg9BK in the pig renal vein, rabbit aorta, and human umbilical vein, three kinin B1 receptor systems. Moreover, this compound was inactive against the effects induced by noradrenaline, 5-hydroxytryptamine, endothelin-1, angiotensin II, substance P, acetylcholine, and histamine in the B2 receptor preparations. Taken together, these results demonstrate that FR 173657 is the first potent nonpeptide B2 receptor antagonist with high affinity, selectivity, and specificity for kinin B2 receptors of different species, including man.

Adult↗

PubMed1995

Characterization of the murine PIG-A promoter region high constitutive PIG-A gene expression in brain.

PIG-A is an X-linked gene that encodes a synthetic element required to initiate glycoinositol phospholipid (GPI) anchor assembly. In this study we characterized genomic sequence flanking the previously identified 5' end of the murine PIG-A gene and analyzed constitutive levels of PIG-A gene expression in vivo in different tissues. We found that the 5'-flanking sequence contains 1) alternative transcriptional start sites at -154 and -34/-33 relative to previously known exon 1 sequence, 2) an MRE and multiple GRE, Ap-2 and Sp-1 consensuses, and 3) a 100-bp-long GC-rich segment bounded by NF-IL6 sites. Our survey of PIG-A mRNA levels in vivo unexpectedly revealed that PIG-A expression levels are 2-4 fold higher in the brain than in other tissues.

Animals↗