Takuro Numaga‐Tomita

β-Arrestin-biased activation of type I angiotensin II receptors improves prognosis of murine pediatric heart failure

Hiroyuki Kawagishi, Takero Nakajima, Toshihide Kashihara, Daisuke Matsuoka et autres

The pharmacological treatment of pediatric heart failure (PHF) remains a long-standing unmet medical need. We previously reported that TRV027, a peptidyl angiotensin type 1 receptor (AT 1 R) agonist that selectively activates β-arrestin over G protein signaling and avoids G protein-mediated vasoconstriction, …

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Reconstitution of depolarization-induced Ca2+ release for validation of skeletal muscle disease mutations and drug discovery

Takashi Murayama, Nagomi Kurebayashi, Takuro Numaga‐Tomita, Takuya Kobayashi et autres

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Novel CACNA1S mutations for malignant hyperthermia enhance depolarization-induced Ca2+ release

Takashi Murayama, Takuro Numaga‐Tomita, Hirotsugu Miyoshi, Keiko Mukaida et autres

Malignant hyperthermia (MH) is a life-threatening genetic disorder in which general anesthetics cause massive Ca2+release from the sarcoplasmic reticulum in skeletal muscle. While most MH mutations have been found in the ryanodine receptor type 1 (RyR1), other genes are also associated with …

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Myocardial TRPC6-mediated Zn2+ influx induces beneficial positive inotropy through β-adrenoceptors

Sayaka Oda, Kazuhiro Nishiyama, Yuka Furumoto, Yohei Yamaguchi et autres

Abstract Baroreflex control of cardiac contraction (positive inotropy) through sympathetic nerve activation is important for cardiocirculatory homeostasis. Transient receptor potential canonical subfamily (TRPC) channels are responsible for α1-adrenoceptor (α1AR)-stimulated cation entry and their upregulation is associated with pathological cardiac remodeling. Whether TRPC …

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A reconstituted depolarization-induced Ca2+ release platform for validation of skeletal muscle disease mutations and drug discovery

Takashi Murayama, Nagomi Kurebayashi, Takuro Numaga‐Tomita, Takuya Kobayashi et autres

In skeletal muscle excitation-contraction (E-C) coupling, depolarization of the plasma membrane triggers Ca2+ release from the sarcoplasmic reticulum (SR), referred to as depolarization-induced Ca2+ release (DICR). DICR occurs through the type 1 ryanodine receptor (RyR1), which physically interacts with the dihydropyridine receptor …

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Inhibition of transient receptor potential cation channel 6 promotes capillary arterialization during post‐ischaemic blood flow recovery

Takuro Numaga‐Tomita, Tsukasa Shimauchi, Yuri Kato, Kazuhiro Nishiyama et autres

BACKGROUND AND PURPOSE: Capillary arterialization, characterized by the coverage of pre-existing or nascent capillary vessels with vascular smooth muscle cells (VSMCs), is critical for the development of collateral arterioles to improve post-ischaemic blood flow. We previously demonstrated that the inhibition of transient …

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Reconstituted depolarization-induced Ca 2+ release platform for skeletal muscle disease mutation validation and drug discovery

Takashi Murayama, Nagomi Kurebayashi, Takuro Numaga‐Tomita, Takuya Kobayashi et autres

Abstract In skeletal muscle excitation-contraction (E-C) coupling, depolarization of the plasma membrane triggers Ca 2+ release from the sarcoplasmic reticulum (SR), referred to as depolarization-induced Ca 2+ release (DICR). DICR occurs via the type 1 ryanodine receptor (RyR1), which physically interacts with …

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A TRPC3/6 Channel Inhibitor Promotes Arteriogenesis after Hind-Limb Ischemia

Tsukasa Shimauchi, Takuro Numaga‐Tomita, Yuri Kato, Hiroyuki Morimoto et autres

Retarded revascularization after progressive occlusion of large conductance arteries is a major cause of bad prognosis for peripheral artery disease (PAD). However, pharmacological treatment for PAD is still limited. We previously reported that suppression of transient receptor potential canonical (TRPC) 6 channel …

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Cytokine receptor gp130 promotes postnatal proliferation of cardiomyocytes required for the normal functional development of the heart

Hiroyuki Kawagishi, Tsutomu Nakada, Takuro Numaga‐Tomita, Maite Larrañaga et autres

Although cardiomyocytes undergo proliferation in the early postnatal period, the regulatory mechanisms and physiological importance of this process have not been clarified. We found that the pharmacological and genetic depletion of gp130 in preweaning mice resulted in significant impairment of cardiomyocyte proliferation, …

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The importance of sympathetic innervation for the postnatal heart development

Takuro Numaga‐Tomita, Hiroyuki Kawagishi, Tsutomu Nakada, Mitsuhiko Yamada

The sympathetic nervous system is important for the adult heart to adapt to the changes in environmental stresses. Besides that, it has been suggested that sympathetic innervation affects postnatal development of the heart. Several lines of evidence have indicated that sympathetic innervation …

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Possible pathophysiological importance of C-terminal tyrosine phosphorylation of CaV1.2 in vessel remodeling

Takuro Numaga‐Tomita, Hiroyuki Kawagishi, Tsutomu Nakada, Mitsuhiko Yamada

Voltage-dependent CaV1.2 L-type calcium channels play a critical role in the regulation blood pressure. Besides, CaV1.2 is implicated to play a pivotal role in chronic vessel remodeling such as atherosclerosis because several clinical trials indicate that CaV1.2 inhibitors delay the progression of …

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Establishment of reconstituted depolarization-induced Ca2+ release platform for drug discovery of skeletal muscle diseases

Takashi Murayama, Nagomi Kurebayashi, Takuro Numaga‐Tomita, Takuya Kobayashi et autres

In skeletal muscle, depolarization of the plasma membrane triggers Ca2+ release from the sarcoplasmic reticulum (SR),referred to as depolarization-induced Ca2+ release (DICR). DICR occurs via the type 1 ryanodine receptor (RyR1), which physically interacts with the dihydropyridine receptor Cav1.1 subunit in specific …

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