Pharmacology of transient receptor potential melastatin channels in the vasculature

Zholos, Alexander

doi:10.1111/j.1476-5381.2010.00649.x

Cited by 41 publications

(35 citation statements)

References 131 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In situ menthol produced Ca 2+ transients that consisted of an initial phasic component, followed by a sustained component. 28, 29 Johnson et al 8 demonstrated that TRPM8 channel activation in the rat artery causes vasoconstriction or vasodilation depending on previous vasomotor tone. However, our results suggest that menthol ultimately reduced the vascular reactivity by inhibiting calcium signaling-mediated RhoA/ROCK pathway inhibition based on of the following reasons: (1) arteries pretreated with menthol showed significant lower reactivity to vasoconstrictors; (2) in the absence of extracellular calcium, agonists only caused weak vasoconstriction, but adding calcium evoked significant vasoconstriction, which was dose dependently inhibited by menthol, indicating that menthol inhibited Ca 2+ influx; (3) the tonic contraction that represents SR Ca 2+ release-mediated RhoA/ROCK activation can be inhibited by menthol; (4) in TRPM8 −/− mice, menthol failed to inhibit U46619-induced vasocontraction and the related vascular calcium signaling.…”

Section: Discussionmentioning

confidence: 99%

Activation of Cold-Sensing Transient Receptor Potential Melastatin Subtype 8 Antagonizes Vasoconstriction and Hypertension Through Attenuating RhoA/Rho Kinase Pathway

et al. 2014

View full text Add to dashboard Cite

Abstract-Environmental cold is a nonmodifiable hypertension risk factor. Transient receptor potential melastatin subtype 8 (TRPM8) is a cold-sensing cation channel that can be activated by menthol, a compound with a naturally cold sensation in mint. Little is known about the effect of TRPM8 activation on vascular function and blood pressure. Here, we report that TRPM8 is abundantly expressed in the vasculature. TRPM8 activation by menthol attenuated vasoconstriction via RhoA/Rho kinase pathway inhibition in wild-type mice, but the effect was absent in TRPM8 −/− mice. Chronic dietary menthol blunted mesenteric arterial constriction and lowered blood pressure in genetic hypertensive rats via inhibition of RhoA/Rho kinase expression and activity in the vivo study. TRPM8 effect was associated with inhibition of intracellular calcium release from the sarcoplasmic reticulum, RhoA/Rho kinase activity, and sustained arterial contraction in the vitro study. Importantly, 8-week chronic menthol capsule treatment moderately lowered systolic blood pressure and diastolic blood pressure in prehypertensive individuals compared with the placebo group. Furthermore, chronic menthol capsule administration also improved flowmediated dilatation in prehypertensive individuals, but not in the placebo group. In conclusion, our study demonstrates that TRPM8 activation by menthol benefits vascular function and blood pressure by inhibiting calcium signaling-mediated RhoA/ Rho kinase activation in the vasculature. These findings add to the evidence that long-term dietary menthol treatment had Materials and Methods Animal TreatmentWe obtained male spontaneously hypertensive rats (SHR) and WistarKyoto rats (WKY) from Charles Rivers Laboratories (Malvern, PA) and obtained TRPM8 −/− mice from the laboratory of Dr Patapoutian. 6To maintain an isogenic strain, heterozygous knockout mice and their wild type (WT) littermates were maintained and used for experiments, as previously described 7 (online-only Data Supplement). Cell CultureVascular smooth muscle cells (VSMCs) were obtained from the thoracic aortas of mice and cultured by the tissue explant method, as previously described 14 (online-only Data Supplement). Intracellular Calcium MeasurementsFluorescence measurements were performed at 510 nm emission, with excitation wavelengths of 340 and 380 nm (Fluoroskan Ascent Fluorometer; Thermo Helsinki, Finland; online-only Data Supplement). Blood Pressure MeasurementAnimals were implanted surgically with telemetric transmitters (Data Sciences International, MN), and 24-hour ambulatory systolic and diastolic pressures were measured by telemetry in conscious unrestrained animals 16 (online-only Data Supplement). Prehypertensive Participant CharacteristicsPrehypertensive participants aged between 45 to 65 years were included in this study. The prehypertension diagnosis was based on systolic blood pressure (SBP) of 120 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg (online-only Data Supplement). Flow-Mediated VasodilationFlow-mediated vasod...

show abstract

Section: Discussionmentioning

confidence: 99%

Activation of Cold-Sensing Transient Receptor Potential Melastatin Subtype 8 Antagonizes Vasoconstriction and Hypertension Through Attenuating RhoA/Rho Kinase Pathway

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In the developing cerebellum, PregS strongly and reversibly enhances glutamate release onto Purkinje cells (PCs) of neonatal rats, an effect that is independent of several PregS‐sensitive targets; namely, NMDA, glycine, α7 nicotinic acetylcholine, and σ1 receptors, as well as voltage‐gated Ca 2+ channels (Zamudio‐Bulcock and Valenzuela 2011). PregS increases glutamate release by enhancing Ca 2+ entrance into pre‐synaptic terminals via a target that is sensitive to La 3+ , a non‐selective agent that modulates a number of TRP channel subtypes and is known to block TRPM3 (Zholos 2010; Zamudio‐Bulcock and Valenzuela 2011). Based on this finding, we hypothesized that TRPM3 channels are expressed at developing glutamatergic synapses on PCs and that they mediate the PregS‐induced enhancement of glutamatergic transmission.…”

mentioning

confidence: 99%

Activation of steroid‐sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats

Zamudio-Bulcock

Everett

Harteneck

et al. 2011

Journal of Neurochemistry

View full text Add to dashboard Cite

The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. Here, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells (PCs). We recently showed that PregS potentiates spontaneous glutamate release onto neonatal PCs during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.

show abstract

“…The TRPM subfamily includes 8 subgroups (TRPM1, TRPM2, TRPM3, TRPM4, TRPM5, TRPM6, TRPM7 and TRPM8), which are considered to have roles in tumorigenesis, cell proliferation and differentiation (11,14). The TRPM subfamily takes its name from the melastatin protein, which is defined as potential tumor suppressor.…”

Section: Introductionmentioning

confidence: 99%

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

et al. 2016

View full text Add to dashboard Cite

Abstract. Urinary bladder cancer is one of the most common malignancies of the urinary tract. Ion channels and calcium homeostasis are involved in almost all basic cellular mechanisms. The transient receptor potential cation channel subfamily M (TRPM) takes its name from the melastatin protein, which is classified as potential tumor suppressor. To the best of our knowledge, there have been no previous studies in the literature investigating the role of these ion channels in bladder cancer. The present study aimed to determine whether bladder cancer is associated with mRNA expression levels of TRPM ion channel genes, and whether there is the potential to conduct further studies to establish novel treatment modalities. The present study included a total of 47 subjects, of whom 40 were bladder cancer patients and 7 were controls. Following the histopathological evaluation for bladder carcinoma, the mRNA and protein expression of TRPM were examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry in tumor and normal tissues, in order to determine whether there is a difference in the expression of these channels in tumor and normal tissues. Immunoreactivity for TRPM2, TRPM4, TRPM7 and TRPM8 was observed in epithelial bladder cells in the two groups. RT-qPCR revealed a significant increase in TRPM7 expression in bladder cancer tissue compared to the controls (healthy bladder tissue), whereas no differences in TRPM2 or TRPM4 expression levels were observed. There were significant reductions in the expression levels of TRPM5 and TRPM8 in bladder cancer tissues. In the present study, the effects of TRP ion channels on the formation of bladder cancer was investigated. This study is instructive for TRPM2, TRPM4, TRPM5, TRPM7 and TRPM8 and their therapeutic role in bladder cancer. The results support the fact that these gens can be novel targets and can also be tested for during the treatment of bladder cancer.

show abstract

Pharmacology of transient receptor potential melastatin channels in the vasculature

Cited by 41 publications

References 131 publications

Activation of Cold-Sensing Transient Receptor Potential Melastatin Subtype 8 Antagonizes Vasoconstriction and Hypertension Through Attenuating RhoA/Rho Kinase Pathway

Activation of Cold-Sensing Transient Receptor Potential Melastatin Subtype 8 Antagonizes Vasoconstriction and Hypertension Through Attenuating RhoA/Rho Kinase Pathway

Activation of steroid‐sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats

Potential role of melastatin-related transient receptor potential cation channel subfamily M gene expression in the pathogenesis of urinary bladder cancer

Contact Info

Product

Resources

About