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Mustard oils and cannabinoids excite sensory nerve fibres through the TRP channel ANKTM1
It is shown that mustard oil depolarizes a subpopulation of primary sensory neurons that are also activated by capsaicin, the pungent ingredient in chilli peppers, and by Δ9-tetrahydrocannabinol, the psychoactive component of marijuana. Expand
Vanilloid receptors on sensory nerves mediate the vasodilator action of anandamide
It is shown that the vasodilator response to anandamide in isolated arteries is capsaicin-sensitive and accompanied by release of calcitonin-gene-related peptide (CGRP), which indicates that the vanilloid receptor may be another molecular target for endogenousAnandamide, besides cannabinoid receptors, in the nervous and cardiovascular systems. Expand
Bradykinin and nerve growth factor release the capsaicin receptor from PtdIns(4,5)P2-mediated inhibition
It is shown that bradykinin- or NGF-mediated potentiation of thermal sensitivity in vivo requires expression of VR1, a heat-activated ion channel on sensory neurons, and biochemical studies suggest that VR1 associates with this complex. Expand
TRP channel activation by reversible covalent modification
Thiol reactive compounds of diverse structure activate TRPA1 in a manner that relies on covalent modification of cysteine residues within the cytoplasmic N terminus of the channel, suggesting an unusual paradigm whereby natural products activate a receptor through direct, reversible, and covalENT protein modification. Expand
Functional Dissociation of μ Opioid Receptor Signaling and Endocytosis Implications for the Biology of Opiate Tolerance and Addiction
It is demonstrated that this regulatory mechanism reveals an independent functional property of opiate drugs that can be distinguished from previously established agonist properties, and this property correlates with agonist propensity to promote physiological tolerance, suggesting a fundamental revision of the role of receptor endocytosis in the biology of opiates drug action and addiction. Expand
Evidence that the nucleotide exchange and hydrolysis cycle of G proteins causes acute desensitization of G-protein gated inward rectifier K+ channels.
A positive regulatory function of R GS4 is uncovered in this study; the opposing effects allow RGS4 to potentiate acute desensitization without compromising GIRK activation. Expand
The anandamide transport inhibitor AM404 activates vanilloid receptors.
In conclusion, AM404 activates native and cloned vanilloid receptors and causes vasodilation in rat isolated hepatic artery contracted with phenylephrine. Expand
The Super-Cooling Agent Icilin Reveals a Mechanism of Coincidence Detection by a Temperature-Sensitive TRP Channel
It is shown that, to achieve full efficacy, icilin requires simultaneous elevation of cytosolic Ca2+, either via permeation through TRPM8 channels or by release from intracellular stores, illustrating the potential for coincidence detection by TRP channels. Expand
Oxidative challenges sensitize the capsaicin receptor by covalent cysteine modification
The capsaicin receptor TRPV1, one of the major transduction channels in the pain pathway, integrates information from extracellular milieu to control excitability of primary nociceptive neurons.Expand
Regulation of IRK3 Inward RectifierK+ Channel by m1 Acetylcholine Receptorand Intracellular Magnesium
It is suggested that the resting Mg2+ level causes chronic inhibition of IRK3 channels, and m1 receptor stimulation may lead to an increase of cytoplasmic Mg 2+ concentration and further channel inhibition, due to the ability of Mg1+ to lead these channels into a prolonged inactivated state. Expand