Using guinea pigs in studies relevant to asthma and COPD

Canning, Brendan J.; Chou, Yang‐Ling

doi:10.1016/j.pupt.2008.01.004

Cited by 97 publications

(84 citation statements)

References 403 publications

(184 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The isolated guinea pig trachea (GPT) is a commonly used model in airway pharmacology, where the receptors for agonists and mediators of mast cell activation are closely similar to those of human airways (6). Accordingly, the antigen-induced contraction in guinea pig airways is caused by the concerted action of cysteinyl-leukotrienes, histamine, and prostanoids (24), mediators also known to cause allergen-induced bronchoconstriction in human subjects with asthma (20).…”

mentioning

confidence: 99%

The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea

Pulkkinen

Manson

Säfholm

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

Pulkkinen V, Manson ML, Säfholm J, Adner M, Dahlén S. The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea. Am J Physiol Lung Cell Mol Physiol 303: L956 -L966, 2012. First published September 7, 2012 doi:10.1152/ajplung.00205.2012.-Activation of taste receptors (TAS2Rs) by bitter taste agonists has been reported to cause bronchodilation. The aim of this study was to extend the information on the effects of bitter taste agonists on responses induced by different contractile mediators in a standard airway physiology preparation. Isometric responses were assessed in guinea pig trachea (GPT). TAS2R agonists were administered either to segments precontracted with different agonists for contraction or given before challenge with the different contractile stimuli, including antigen in tissues from ovalbumin-sensitized animals. TAS2R mRNA expression on GPT epithelium and smooth muscle was measured with real-time PCR. Denatonium, chloroquine, thiamine, and noscapine induced concentration-dependent relaxations (R max: 98.3 Ϯ 1.6, 100.0 Ϯ 0.0, 100.0 Ϯ 0.0, and 52.3 Ϯ 1.1% of maximum, respectively, in the presence of indomethacin) in segments precontracted with carbachol. The receptors for denatonium (TAS2R4, TAS2R10) and chloroquine (TAS2R3, TAS2R10) were expressed in GPT. Whereas denatonium selectively inhibited contractions induced by carbachol, chloroquine uniformly inhibited contractions evoked by prostaglandin E 2, the thromboxane receptor agonist U-46619, leukotriene D 4, histamine, and antigen. The effects of denatonium, but not those of chloroquine, were partly inhibited by blockers of the large Ca 2ϩ -activated K ϩ channels and decreased by an increase of the level of precontraction. In conclusion, TAS2R agonists mediated strong relaxations and substantial inhibition of contractions in GPT. Chloroquine and denatonium had distinct patterns of activity, indicating different signaling mechanisms. The findings reinforce the hypothesis that TAS2Rs are potential targets for the development of a new class of more efficacious agonists for bronchodilation. bronchodilation; asthma; prostaglandins; airway smooth muscle BITTER TASTE-SENSING TYPE 2 receptors (TAS2Rs) are G proteincoupled receptors (GPCRs) on cell surface that mediate gustatory taste perception on the tongue (16). The properties of TAS2Rs are different from many other GPCRs, as the receptors are promiscuous and capable of binding a wide range of compounds with relatively low specificity and affinity (16). TAS2Rs have recently been suggested to have important extraoral functions in the respiratory and gastrointestinal tracts (4, 11). In the human airway epithelium, TAS2Rs are expressed on the solitary chemosensory cells (25,26) and ciliated epithelial cells (23), where they sense chemical irritation and promote ciliary beat frequency, respectively. Thus TAS2Rs may be protective and part of the defense against inhaled noxious compounds.Recently airway smooth muscle cells were foun...

show abstract

mentioning

confidence: 99%

The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea

Pulkkinen

Manson

Säfholm

et al. 2012

American Journal of Physiology-Lung Cellular and Molecular Phys

View full text Add to dashboard Cite

show abstract

“…Moreover, we show that TLR2/6 and TLR9 agonists exert an antiviral effect that is conserved across species, and we demonstrate two therapeutic delivery methods (nasal and inhalational) applicable to future drug development in humans. Furthermore, guinea pig airway nerve function and anatomy resemble those in humans, making it more applicable than a murine model for investigating in vivo dynamic airway responsiveness to a variety of stimuli (35).…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptor–2/6 and Toll-Like Receptor–9 Agonists Suppress Viral Replication but Not Airway Hyperreactivity in Guinea Pigs

Drake

Evans

Dickey

et al. 2013

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Respiratory virus infections cause airway hyperreactivity (AHR). Preventative strategies for virus-induced AHR remain limited. Toll-like receptors (TLRs) have been suggested as a therapeutic target because of their central role in triggering antiviral immune responses. Previous studies showed that concurrent treatment with TLR2/6 and TLR9 agonists reduced lethality and the microbial burden in murine models of bacterial and viral pneumonia. This study investigated the effects of TLR2/6 and TLR9 agonist pretreatment on parainfluenza virus pneumonia and virus-induced AHR in guinea pigs in vivo. Synthetic TLR2/6 lipopeptide agonist Pam 2 CSK 4 and Class C oligodeoxynucleotide TLR9 agonist ODN2395, administered in combination 24 hours before virus infection, significantly reduced viral replication in the lung. Despite a fivefold reduction in viral titers, concurrent TLR2/6 and TLR9 agonist pretreatment did not prevent virus-induced AHR or virus-induced inhibitory M2 muscarinic receptor dysfunction. Interestingly, the TLR agonists independently caused non-M2-dependent AHR. These data confirm the therapeutic antiviral potential of TLR agonists, while suggesting that virus inhibition may be insufficient to prevent virus-induced airway pathophysiology. Furthermore, TLR agonists independently cause AHR, albeit through a distinctly different mechanism from that of parainfluenza virus.

show abstract

“…There is an abundance of reviews emphasizing the versatility of guinea pigs as research models in general [5], [6], [7], [8], [9], [10], [11], [12] and [13] or with reference to infectious diseases and vaccination [14], [15], [16], [17], [18], [19], [20], [21] and [22], with a strong focus on tuberculosis research [4], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33] and [34]. Guinea pigs represent the "gold standard" among small animal models to test the efficiency of new and established vaccines against tuberculosis [35], [36] and [37], and are useful for vaccination studies against other diseases [38], [39] and [40], but most authors agree that the limited availability of immunological reagents in this species strongly restricts its usefulness for modern experimental approaches.…”

Section: Introductionmentioning

confidence: 99%

Tools for cellular immunology and vaccine research the in the guinea pig: Monoclonal antibodies to cell surface antigens and cell lines

Schäfer

Bürger

2012

Vaccine

View full text Add to dashboard Cite

Using guinea pigs in studies relevant to asthma and COPD

Cited by 97 publications

References 403 publications

The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea

The bitter taste receptor (TAS2R) agonists denatonium and chloroquine display distinct patterns of relaxation of the guinea pig trachea

Toll-Like Receptor–2/6 and Toll-Like Receptor–9 Agonists Suppress Viral Replication but Not Airway Hyperreactivity in Guinea Pigs

Tools for cellular immunology and vaccine research the in the guinea pig: Monoclonal antibodies to cell surface antigens and cell lines

Contact Info

Product

Resources

About