Cooling‐induced contraction of the rat gastric fundus: Mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho‐kinase activation

Mustafa, Seham; Oriowo, Mabayoje A.

doi:10.1111/j.1440-1681.2005.04273.x

Cited by 42 publications

(41 citation statements)

References 34 publications

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“…However, the expression and role of TRPM8 in the GI tract and its involvement in the clinical effects of herbal medicines are still controversial. TRPM8 mRNA was detected in the fundus (and colon) of rat and was implicated in cooling-induced contractions of fundic muscle strips (Mustafa and Oriowo, 2005). Zhang et al also found TRPM8 mRNA in murine NG, small intestinal and stomach mucosa but Penuelas et al failed to confirm its expression although the same primer pairs were used (Zhang et al, 2004;Penuelas et al, 2007).…”

Section: Trpm Channelsmentioning

confidence: 95%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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The members of the superfamily of transient receptor potential (TRP) cation channels are involved in a plethora of cellular functions. During the last decade, a vast amount of evidence is accumulating that attributes an important role to these cation channels in different regulatory aspects of the alimentary tract. In this review we discuss the expression patterns and roles of TRP channels in the regulation of gastrointestinal motility, enteric nervous system signalling and visceral sensation, and provide our perspectives on pharmacological targeting of TRPs as a strategy to treat various gastrointestinal disorders. We found that the current knowledge about the role of some members of the TRP superfamily in neurogastroenterology is rather limited, whereas the function of other TRP channels, especially of those implicated in smooth muscle cell contractility (TRPC4, TRPC6), visceral sensitivity and hypersensitivity (TRPV1, TRPV4, TRPA1), tends to be well established. Compared with expression data, mechanistic information about TRP channels in intestinal pacemaking (TRPC4, TRPC6, TRPM7), enteric nervous system signalling (TRPCs) and enteroendocrine cells (TRPM5) is lacking. It is clear that several different TRP channels play important roles in the cellular apparatus that controls gastrointestinal function. They are involved in the regulation of gastrointestinal motility and absorption, visceral sensation and visceral hypersensitivity. TRP channels can be considered as interesting targets to tackle digestive diseases, motility disorders and visceral pain. At present, TRPV1 antagonists are under development for the treatment of heartburn and visceral hypersensitivity, but interference with other TRP channels is also tempting. However, their role in gastrointestinal pathophysiology first needs to be further elucidated.

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Section: Trpm Channelsmentioning

confidence: 95%

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Boesmans

Owsianik

Tack

et al. 2010

British J Pharmacology

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“…It has been reported that TRPM8 mRNA or protein or both are expressed in the prostate, sensory neurons, gastric fundus, vascular smooth muscle, liver and urogenital organs [19,30,31,32,33]. Several reports have indicated that TRPM8 is expressed not only in the plasma membrane, but also in the endoplasmic reticulum membrane.…”

Section: Discussionmentioning

confidence: 99%

Menthol Induces Cell Death via the TRPM8 Channel in the Human Bladder Cancer Cell Line T24

Wang²,

Yang³

et al. 2009

Oncology

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Objective: Growing evidence has shown that menthol has potent anticancer activity in various human cancers via the transient receptor potential melastatin 8 (TRPM8)-dependent pathway or in a TRPM8-independent manner. However, its effect on bladder cancer remains obscure. In the present investigation, we examined the expression of TRPM8 and the role of menthol in cells of the human bladder cancer cell line T24. Methods: RT-PCR, Western blotting and immunocytochemistry were used to confirm the expression and location of TRPM8 in T24 cells. Results: TRPM8 was highly expressed in T24 cells and located in both the cell membrane and cytoplasm. With the use of small interfering RNA to silence the expression of TRPM8, we found that menthol could increase the concentration of intracellular calcium and decrease cell viability via the TRPM8 channel in T24 cells. We also found that menthol could induce cell death through TRPM8 in T24 cells, rather than cell cycle arrest or apoptosis. Moreover, the detection of mitochondrial membrane potential showed that menthol could induce mitochondrial membrane depolarization in T24 cells. Conclusions: In the present study, we demonstrated that menthol can induce mitochondrial membrane depolarization via the TRPM8 channel in cells of the human bladder cancer cell line T24, resulting in cell death. It would be helpful to explore the precise mechanism of action of menthol in bladder cancer with a view to its possible use as intravesical chemotherapy.

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“…34 Antagonizing ROCK using fasudil lowers blood pressure in hypertensive patients. 35,36 Mustafa et al 9 reported that TRPM8-induced gastric fundus contraction is associated with the RhoA/ROCK pathway. Although menthol can inhibit the vasoconstriction by blocking L-type calcium channel-induced calcium influx at several vessel beds, 30 it remains to be determined whether menthol has an effect on calcium release from SR and its underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…7 Johnson et al 8 demonstrated that menthol-induced TRPM8 activation regulates vascular tone. Mustafa et al 9 reported…”

mentioning

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

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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...

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Cooling‐induced contraction of the rat gastric fundus: Mediation via transient receptor potential (TRP) cation channel TRPM8 receptor and Rho‐kinase activation

Cited by 42 publications

References 34 publications

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

TRP channels in neurogastroenterology: opportunities for therapeutic intervention

Menthol Induces Cell Death via the TRPM8 Channel in the Human Bladder Cancer Cell Line T24

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

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