Yoichi Inada

Effects of dopamine d2 receptor agonists in a pituitary transplantation-induced hyperprolactinaemia/anovulation model in rats.

1. In the present study, we investigated the effects of hyperprolactinaemia, induced by transplantation of anterior pituitary glands under the kidney capsule in female rats, on the relationship between serum and pituitary concentrations of the gonadotropins and on the oestrous cycle.

KRH-594, A New Angiotensin At1 Receptor Antagonist, Prevents End-Organ Damage In Stroke-Prone Spontaneously Hypertensive/Izm Rats

1. In the present study, we examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, would stop the progression of renal failure and end‐organ damage and improve the survival rate in salt‐loaded stroke‐prone spontaneously hypertensive rats (SHRSP/Izm).

Krh-594, A New Angiotensin At1 Receptor Antagonist, Ameliorates Nephropathy And Hyperlipidaemia In Diabetic Spontaneously Hypertensive Rats

1. We examined whether KRH‐594, a new angiotensin AT1 receptor antagonist, ameliorates the progression of diabetic nephropathy and hyperlipidaemia in streptozotocin (STZ)‐induced diabetic unilateral nephrectomized spontaneously hypertensive rats (DM‐1K‐SHR) or not.

Binding of KRH-594, an antagonist of the angiotensin II type 1 receptor, to cloned human and rat angiotensin II receptors.

We studied the binding properties of KRH‐594, a new selective antagonist of angiotensin II (AII) type 1 (AT1) receptors, to rat liver membranes and to recombinant AT1 and AT2 receptors. Preincubation of rat liver membranes with KRH‐594 produced maximal inhibition of [125I]‐AII binding when the preincubation time was 1–2 h. Preincubation with KRH‐594 for 2 h decreased the Bmax value and increased the Kd value. For human AT1, human AT2, rat AT1A and rat AT1B receptors, the Ki values for KRH‐594 were 1.24, 9360, 0.67, and 1.02 nm, respectively. The rank order of Ki values for human AT1 receptors was KRH‐594 >> EXP3174 > candesartan=AII. The order of specificities for human AT1 and AT2 receptors was candesartan > EXP3174 > KRH‐594. Although a 2‐h preincubation of human AT2 receptors with KRH‐594 (30 µm) or CGP 42112 (a selective AT2 receptor antagonist; 0.3 nm) inhibited binding of [125I]‐AII, the suppression by KRH‐594 was not significant. These results indicate that KRH‐594 binds potently to AT1 receptors in an insurmountable manner, and that at a very high dose (30 µm) it may also bind to AT2 receptors, but in a surmountable manner.

Heterogeneous Distribution Of β-Adrenoceptors and Muscarinic Receptors In The Sinoatrial Node And Right Atrium Of The Dog

1. The pacemaker site is known to shift away from the sinoatrial (SA) node in response to autonomic stimuli.

Rat homologue of the human Mr 110 000 antigen is the protein that expresses widely in various tissues

The rat homologue of the human M(r) 110000 antigen, which cross-reacts with anti-carcinoembryonic antigen antibodies, was isolated from a rat lung cDNA library. The deduced amino acid sequence revealed a signal peptide, cysteine-rich and immunoglobulin-like region, serine-threonine region, and N-glycosylation sites in the extracellular portion. Northern blot analysis demonstrated a wide distribution of the mRNA in adult rat tissues and A10 rat vascular smooth muscle cells. Therefore, the rat homologue of the human M(r) 110000 antigen may be a receptor or a cell adhesion molecule rather than a specific carcinogenic antigen.

Erratum to “Relationship between ligand binding and YIPP motif in the C-terminal region of human AT1 receptor” [Biochim. Biophys. Acta 1640 (2003) 33–41]

0167-4889/

Novel hyperprolactinemia and hyperprolactinemic anovulation model using the cynomolgus monkey (Macaca fascicularis)

see front matter D 2003 Elsevier Science B.V. All rights reserved doi:10.1016/S0167-4889(03)00066-1

Molecular cloning and expression of HRLRRP, a novel heart-restricted leucine-rich repeat protein

doi of original article: 10.1016/S0167-4889(02)00400-7. * Corresponding author. Fax: +81-263-37-3085. E-mail address: nakane@sch.md.shinshu-u.ac.jp (T. Nakane). Fig. 7. AII-induced rapid rises in intracellular Ca + concentration. (A) Typical recording and concentration dependency of AII-induced peak Ca + responses in COS-7 cells expressingWT FLAG-AT1 receptor. Data are presented as the mean F S.E. from four experiments. (B) AII (100 nM)-induced peak Ca 2 + responses in WTand mutant FLAG-AT1 receptors. Data are presented as the mean F S.E. from seven to eight experiments with no antagonist, or as the meanF S.E. from three to four experiments with 1 AM KRH-594 as an AT1 receptor antagonist. P< 0.05 vs. WT with no treatment; P < 0.01 05 vs. WT with no treatment; *P < 0.05 vs. corresponding ‘‘no treatment’’; **P< 0.01 vs. correspoding ‘‘no treatment’’. The publisher regrets that in the left-hand panel of Fig. 7A of the above paper, the label AII (100 nm) should read AII (100 nM). The correct figure is shown below.

Effects of the new angiotensin II type 1 receptor antagonist KRH-594 on several types of experimental hypertension

We investigated the relationship between the menstrual cycle and hormone levels in cynomolgus monkeys, and developed a sulpiride-induced hyperprolactinemic anovulation model. On this study, we demonstrated the usefulness of the commercial human prolactin immunoradiometric assay kit for the measurement of cynomolgus monkey serum samples. In the normal menstrual cycle of the cynomolgus monkey, serum prolactin concentrations were not significantly different between luteal and follicular phases. However, the serum prolactin concentration tended to elevate at the ovulation stage. And serum progesterone began to increase after an estradiol surge, and then declined before the ensuing preovulatory rise in estradiol. During the luteal phase, the serum concentration of progesterone was elevated. Moreover, we aimed to develop an anovulation model, using sulpiride-induced hyperprolactinemia in the cynomolgus monkey. The serum prolactin level gradually increased during the twice-daily administration of sulpiride, and the drug produced as big a response at 5 mg/kg. In this study, the length of the menstrual cycle was approximately 29 days in normal cynomolgus monkeys. When treatment with sulpiride had been continued for more than one month, serum progesterone and estradiol levels fell to within the range seen in the follicular phase of the normal cycle, and the absence of ovulation was recognized by laparoscopy. Moreover, in this period we found that amenorrhea or anovulatory menstruation in the experimental animals. We could produce an anovulatory model induced by sulpiride repeatedly administered over a long time period. Our findings suggest that the cynomolgus monkey is useful as a endocrinological model that uses prolactin as a parameter and as an anovulatory model; thus, it could be a useful model for the hyperprolactinemic amenorrhea and/or anovulation seen in humans.