Biomedical subjects

Mitsuhiko Yamada

Publications and source records attributed to Mitsuhiko Yamada.

41 records · Page 3Linked to original sources

PubMed2003

[Pharmacogenomics and antidepression research].

Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool we have previously identified hundreds of cDNA fragments as antidepressant related genes (ADRGs). Some of these candidate genes may encode common functional molecules induced by chronic antidepressant treatment. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Novel biological approaches beyond the "monoamine hypothesis" are expected to evoke paradigm shifts in the future of antidepressant research.

Animals↗

PubMed2002

beta-Adrenergic modulation of prepulse facilitation of L-type calcium channels in rabbit ventricular myocytes.

It is reported that strong depolarization augments cardiac L-type Ca currents by inducing the special gating mode with long-lasting openings (mode 2) (Pietrobon and Hess Nature 346:651-655, 1990). However, a prepulse to +90 mV did not obviously facilitate the current at 0 mV in rabbit ventricular myocytes as measured in the whole-cell configuration of the patch-clamp method in the presence of 2 mM BaCl(2) in the external solution. In the presence of isoproterenol (1 microM), the inactivation during the prepulse was attenuated, and the prepulse evoked facilitation. However, the current at 0 mV whose amplitude was normalized to the extent of the inactivation at +90 mV still exhibited greater facilitation in the presence than in the absence of isoproterenol. In the cell-attached configuration with 110 mM BaCl(2) in pipettes, repolarization from +110 to +20 mV yielded mainly blank sweeps (mode 0) and only occasionally mode 2, leading to no facilitation of the average current. Isoproterenol augmented the prepulse-induced increase in mode 2, reciprocally inhibited that in mode 0, and increased the fraction of mode 2 in non-blank sweeps after the prepulse. Therefore, beta-adrenergic stimulation favors mode 2 rather than mode 0 at strongly depolarized potentials, thereby promoting the prepulse facilitation and attenuating the inactivation of cardiac L-type Ca currents.

Adrenergic beta-Agonists↗

PubMed2002

Functional genomics and depression research. Beyond the monoamine hypothesis.

Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Functional genomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool we have previously identified more than 300 cDNA fragments as antidepressant related genes and from these, original cDNA microarrays were developed. Some of these candidate genes may encode common functional molecules induced by chronic antidepressant treatment. Defining the roles of these genes in drug-induced neural plasticity is likely to transform the course of research on the biological basis of depression. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Novel biological approaches beyond the "monoamine hypothesis" are expected to evoke paradigm shifts in the future of depression research.

Animals↗

PubMed2002

The role of muscarinic K(+) channels in the negative chronotropic effect of a muscarinic agonist.

Acetylcholine causes bradycardia through M2 muscarinic receptors in sinoatrial node cells. I examined with electrocardiogram how the muscarinic K(+) (K(ACh)) channel participates in the sinus bradycardia induced by a muscarinic agonist in the Langendorff preparation of rabbit hearts. In the presence of 100 nM propranolol, 1 nM to 10 microM carbachol (CCh) induced sinus bradycardia in a concentration-dependent manner. Tertiapin (100 or 300 nM), which selectively blocks K(ACh) channels in cardiac myocytes, significantly inhibited the effect of > or =300 nM but not < or =100 nM CCh. The effect of CCh was divided into tertiapin-sensitive and -insensitive components. The former component was induced by >100 nM CCh in a concentration-dependent manner and accounted for approximately 75% of the maximum effect of CCh. The K(ACh) channel in atrial myocytes was also activated by this range of concentrations of CCh as measured with the patch-clamp method. The tertiapin-insensitive component was induced by 1 to 300 nM CCh in a concentration-dependent manner and accounted for approximately 25% of the maximum effect of CCh. The sinus rate in the presence of 1 microM CCh and 300 nM tertiapin was similar to that in the presence of 2 mM CsCl, a blocker of the hyperpolarization-activated I(f) current. Furthermore, no tertiapin-insensitive component existed in the presence of 2 mM CsCl. Therefore, the negative chronotropic effect of > or =300 nM CCh is mainly mediated by K(ACh) channels, whereas that of < or =100 nM CCh may result from suppression of the I(f) current.

Animals↗

PubMed2002

[Pharmacogenomics and future antidepressant research].

Although antidepressants have been used clinically for more than 50 years, no consensus has been reached concerning their precise molecular mechanism of action. Pharmacogenomics is a powerful tool that can be used to identify genes affected by antidepressants or by other effective therapeutic manipulations. Using this tool we have previously identified more than 300 cDNA fragments as antidepressant-related genes. Some of these candidate genes may encode common functional molecules induced by chronic antidepressant treatment. Defining the roles of these molecules in drug-induced neural plasticity is likely to transform the course of research on the biological basis of antidepressants. Such detailed knowledge will have profound effects on the diagnosis, prevention, and treatment of depression. Novel biological approaches beyond the "monoamine hypothesis" are expected to evoke paradigm shifts in the future of antidepressant research.

Antidepressive Agents↗