Cloning and functional characterization of the guinea pig vanilloid receptor 1

Savidge, Jonathan R.; Davis, Clare; Shah, Kirti; Colley, Sian; Phillips, Elsa; Ranasinghe, Sam; Winter, Janet; Kotsonis, Peter; Rang, H P; McIntyre, Peter

doi:10.1016/s0028-3908(02)00122-3

Cited by 97 publications

(70 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Capsazepine is an effective capsaicin antagonist at TRPV1 from rat, human and guinea pig. While capsazepine blocks the responses of human and guinea pig TRPV1 to low pH and heat, we observed that it only weakly inhibits these responses in cells expressing rat TRPV1 in [Ca 2ϩ ] i assays (1,10). This pharmacological difference of capsazepine inhibition has also been observed with native receptors in rat and guinea pig sensory neurons (14 -16).…”

supporting

confidence: 62%

“…In addition to these agonists, TRPV1 is activated by low pH (Ͻ6.5) and by noxious heat (Ͼ42°C) (7)(8)(9) We have shown differences in the pharmacological properties of the mammalian orthologues of TRPV1 (1,10). Human, rat and guinea pig TRPV1 expressed in mammalian cells can be similarly activated by capsaicin, low pH, and noxious heat (Ͼ42°C) (1,2,10). However, the competitive capsaicin antagonist capsazepine (11,12) and the agonists PPAHV and RTX show species-specific differences (1,10,13).…”

mentioning

confidence: 99%

“…Human, rat and guinea pig TRPV1 expressed in mammalian cells can be similarly activated by capsaicin, low pH, and noxious heat (Ͼ42°C) (1,2,10). However, the competitive capsaicin antagonist capsazepine (11,12) and the agonists PPAHV and RTX show species-specific differences (1,10,13). Capsazepine is an effective capsaicin antagonist at TRPV1 from rat, human and guinea pig.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of Species-specific Determinants of the Action of the Antagonist Capsazepine and the Agonist PPAHV on TRPV1

Phillips

Reeve

Bevan

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

The vanilloid receptor 1 (VR1 or TRPV1) ion channel is activated by noxious heat, low pH and by a variety of vanilloid-related compounds. The antagonist, capsazepine is more effective at inhibiting the human TRPV1 response to pH 5.5 than the rat TRPV1 response to this stimulus. Mutation of rat TRPV1 at three positions in the S3 to S4 region, to the corresponding human amino acid residues I514M, V518L, and M547L decreased the IC 50 values for capsazepine inhibition of the pH 5.5 response from >10,000 nM to 924 ؎ 241 nM in [Ca 2؉ ] i assays and increased capsazepine inhibition of the capsaicin response to levels seen for human TRPV1. We have previously noted that phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV) is a strong agonist of rat TRPV1 but not human TRPV1 in [Ca 2؉ ] i assays (1). Mutation of methionine 547 in S4 of rat TRPV1 to leucine, found in human TRPV1 (M547L), reduced the ability of PPAHV to activate TRPV1 by ϳ20-fold. The reciprocal mutation of human TRPV1 (L547M) enabled the human receptor to respond to PPAHV. These mutations did not significantly affect the agonist activity of capsaicin, resiniferatoxin (RTX) or olvanil in [Ca 2؉ ] i assays. Introducing the equivalent mutation into guinea pig TRPV1 (L549M) increased the agonist potency of PPAHV by > 10-fold in the [Ca 2؉ ] i assay and increased the amplitude of the evoked current. The rat M547L mutation reduced the affinity of RTX binding. Thus, amino acids within the S2-S4 region are important sites of agonist and antagonist interaction with TRPV1.The vanilloid compound capsaicin, the hot substance in chili peppers, activates a specific receptor on sensory nerves termed the vanilloid receptor 1 (VR1 or TRPV1), 1 which was cloned and initially characterized by Caterina et al. (2). TRPV1 is activated by a number of other compounds containing vanillyl groups (see Fig. 1) such as the capsaicin analogue olvanil (3), the phorbol compounds resiniferatoxin (RTX), and phorbol 12-phenyl-acetate 13-acetate 20-homovanillate (PPAHV) (4). A number of endogenous lipid molecules, such as anandamide (5) and lipoxygenase products, including some hydroxyeicosatetraenoic acids and leukotriene B 4 (6), which may be produced during inflammation also activate TRPV1. In addition to these agonists, TRPV1 is activated by low pH (Ͻ6.5) and by noxious heat (Ͼ42°C) (7-9)We have shown differences in the pharmacological properties of the mammalian orthologues of TRPV1 (1, 10). Human, rat and guinea pig TRPV1 expressed in mammalian cells can be similarly activated by capsaicin, low pH, and noxious heat (Ͼ42°C) (1, 2, 10). However, the competitive capsaicin antagonist capsazepine (11, 12) and the agonists PPAHV and RTX show species-specific differences (1, 10, 13). Capsazepine is an effective capsaicin antagonist at TRPV1 from rat, human and guinea pig. While capsazepine blocks the responses of human and guinea pig TRPV1 to low pH and heat, we observed that it only weakly inhibits these responses in cells expressing rat TRPV1 in [Ca 2ϩ ] i assays (1, 10). This pha...

show abstract

supporting

confidence: 62%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Identification of Species-specific Determinants of the Action of the Antagonist Capsazepine and the Agonist PPAHV on TRPV1

Phillips

Reeve

Bevan

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…These studies revealed that tachykinin and capsaicin receptor pharmacology is very similar in human and guinea pig airways, and in both species tachykinins are metabolized in the lung by neutral endopeptidase [253,[288][289][290][291]. Despite many important and fundamental discoveries relating to afferent nerve excitability, the axon reflex and tachykinin and capsaicin receptor pharmacology, it now seems likely that the axon reflex as it manifests in the lungs of guinea pigs and rats is not present in the human lung.…”

Section: Axon Reflexmentioning

confidence: 99%

Using guinea pigs in studies relevant to asthma and COPD

Canning

Chou

2008

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

The guinea pig has been the most commonly used small animal species in preclinical studies related to asthma and COPD. The primary advantages of the guinea pig are the similar potencies and efficacies of agonists and antagonists in human and guinea pig airways and the many similarities in physiological processes, especially airway autonomic control and the response to allergen. The primary disadvantages to using guinea pigs are the lack of transgenic methods, limited numbers of guinea pig strains for comparative studies and a prominent axon reflex that is unlikely to be present in human airways. These attributes and various models developed in guinea pigs are discussed.

show abstract

“…Caterina and co-workers cloned TRPV1 from a rat sensory neuron cDNA library and showed that the receptor is expressed in both the dorsal root (DRG) and trigeminal ganglia (TG) [24]. TRPV1 has also been cloned from humans [25], guinea pigs [26], rabbits [27], mouse mice [28] and dogs [29].…”

Section: Trpvs: a Brief Overviewmentioning

confidence: 99%

Is TRPV1 a useful target in respiratory diseases?

Takemura

Quarcoo

Niimi

et al. 2008

Pulmonary Pharmacology & Therapeutics

View full text Add to dashboard Cite

This review focuses on the transient receptor potential vanilloid 1 (TRPV1). TRPV1 is a non-selective cation channel predominantly expressed in the cell membranes of sensory afferent fibers, which are activated multi-modally. In the mammalian respiratory system, immunohistochemical and electrophysiological studies have revealed heterogeneous localizations of TRPV1 channels in the airways and their presence in pleural afferents. TRPV1 channels in afferents are not only involved with sensory inputs, but also release several neuropeptides upon stimulation. These processes trigger pathophysiological effects (e.g. reflex bronchoconstriction, hypersecretion, cough, etc.) that cause various symptoms of airway diseases.Recent studies have identified several endogenous and exogenous substances that can activate TRPV1 in the lung. Because of its key role in initiating inflammatory processes, TRPV1 receptor antagonists have been proposed as therapeutic candidates. Therefore, a critical update of recent therapeutic results is also given in this review.

show abstract

Cloning and functional characterization of the guinea pig vanilloid receptor 1

Cited by 97 publications

References 18 publications

Identification of Species-specific Determinants of the Action of the Antagonist Capsazepine and the Agonist PPAHV on TRPV1

Identification of Species-specific Determinants of the Action of the Antagonist Capsazepine and the Agonist PPAHV on TRPV1

Using guinea pigs in studies relevant to asthma and COPD

Is TRPV1 a useful target in respiratory diseases?

Contact Info

Product

Resources

About