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Biomedical subjects

I Akiba

Publications and source records attributed to I Akiba.

13 recordsLinked to original sources
PubMed1989

Selective effector coupling of muscarinic acetylcholine receptor subtypes.

Attempts have been made by means of recombinant DNA technology to understand the molecular basis of the functional heterogeneity of the muscarinic acetylcholine receptor (mAChR). Molecularly defined mAChR subtypes have been produced from the cloned DNAs in Xenopus oocytes and NG108-15 neuroblastoma-glioma hybrid cells as transient and stable expression systems, respectively, and agonist-induced cellular responses have been examined. The results obtained provide evidence that mAChR subtypes are selectively coupled with different effector systems, albeit not exclusively.

Animals↗
PubMed1988

Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling.

Chimaeric muscarinic acetylcholine receptors (mAChR) in which corresponding portions of mAChR I and mAChR II are replaced with each other have been produced in Xenopus oocytes by expression of cDNA constructs encoding them. Functional analysis of the chimaeric mAChRs indicates that a region mostly comprising the putative cytoplasmic portion between the proposed transmembrane segments V and VI is involved in selective coupling of mAChR I and mAChR II with different effector systems. In contrast, the exchange of this region between mAChR I and mAChR II does not significantly affect the antagonist binding properties of the two mAChR subtypes.

Animals↗
PubMed1988

Different sensitivities to agonist of muscarinic acetylcholine receptor subtypes.

Muscarinic acetylcholine receptor (mAChR) III expressed in Xenopus oocytes, like mAChR I, mediates activation of a Ca2+-dependent Cl- current, whereas mAChR IV, like mAChR II, principally induces activation of Na+ and K+ currents in a Ca2+-independent manner. mAChR III has a sensitivity to agonist of about one order of magnitude higher than that of mAChR I in mediating the Ca2+-dependent current response in Xenopus oocytes and in stimulating phosphoinositide hydrolysis in NG108-15 neuroblastoma-glioma hybrid cells. The agonist-binding affinity of mAChR III is also about one order of magnitude higher than that of mAChR I.

Acetylcholine↗
PubMed1988

Selective coupling with K+ currents of muscarinic acetylcholine receptor subtypes in NG108-15 cells.

The primary structures of two muscarinic acetylcholine receptor (mAChR) species, designated as mAChR I and mAChR II, have been elucidated by cloning and sequence analysis of DNAs complementary to the porcine cerebral and cardiac messenger RNAs, respectively. mAChR I and mAChR II expressed in Xenopus oocytes differ from each other both in acetylcholine-induced response and in antagonist binding properties. These results, together with the differential tissue location of the two mAChR mRNAs, have indicated that pharmacologically distinguishable subtypes of the mAChR represent distinct gene products. The primary structures of two additional mammalian mAChR species, designated as mAChR III and mAChR IV, have subsequently been deduced from the nucleotide sequences of the cloned cDNAs or genomic DNAs. We report here that mAChR I and mAChR III expressed in NG108-15 neuroblastoma-glioma hybrid cells, but not mAChR II and mAChR IV, efficiently mediate phosphoinositide hydrolysis, activation of a Ca2+-dependent K+ current and inhibition of the M-current, a voltage-dependent K+ current sensitive to muscarinic agonists.

Acetylcholine↗
PubMed1983

Narcotic physical dependence and urinary sex-dependent low molecular weight proteins in male rats.

The relationship between urinary excretion of sex-dependent low molecular weight proteins (LMWP) in male rats and narcotic dependence is described in this study. Rats were intermittently infused with narcotics at one hour intervals through an implanted intravenous cannula. Development of physical dependence on morphine, pethidine, and pentazocine was detected by withdrawal signs including body weight loss and abnormal behaviors after naloxone challenge. In these animals, a significant decrease in urinary LMWP excretion was found following the second day of each drug treatment without significant changes in albumin excretion, and this decrease was observed continuously throughout the experiment. The markedly decreased level of LMWP recovered to the control level within 7 d after withdrawal of the drugs. These results suggest that the decrease in urinary excretion of sex-dependent LMWP in male rats is a phenomenon closely related to narcotic dependence.

Animals↗
PubMed1983

A new approach for assessment of narcotic physical dependence using urinary sex-dependent low molecular weight proteins in male rats.

Attempts have been made to examine the relationship between urinary excretion of sex-dependent low molecular weight proteins found only in male rats (LMWP) and morphine physical dependence. Chronic administration of morphine produced a dose-related decrease in urinary LMWP excretion, which was correlated to the intensity of withdrawal signs including body weight loss and abnormal behaviors recognized after naloxone challenge. Furthermore, a statistically high correlation was obtained between the decrease in urinary LMWP excretion and the loss of body weight precipitated by naloxone challenge. LMWP was identified immunologically in the livers, kidneys, and sera using an antibody against purified LMWP. The serum level of LMWP was increased rapidly following bilateral nephrectomy. After chronic treatment with morphine, the LMWP content in the livers, kidneys, and sera were decreased. These findings indicate that the decrease in urinary LMWP excretion induced by chronic administration of morphine can be a useful parameter to assess the development of physical dependence on narcotics on the peripheral level without requiring drug withdrawal and naloxone challenge. This decrease in urinary LMWP may be caused by the inhibition of LMWP synthesis in the liver.

Animals↗
PubMed1983

[Relationship between the decrease in urinary sex-dependent low molecular weight proteins by morphine and hormonal parameters in male rats].

The relationship between the decrease in urinary sex-dependent low molecular weight proteins (LMWP), which exist only in the male rat, and the serum levels of some hormones were examined in this study. Castration of male rats reduced the urinary excretion of LMWP by about 50%. Replacement therapy with testosterone increased the urinary LMWP excretion. Adrenalectomy did not affect the urinary excretion of LMWP. In the adrenalectomized rat, however, corticosterone increased LMWP excretion. Therefore, it is considered that testosterone and corticosterone play a part in the urinary excretion of LMWP under physiological conditions and that the effect of testosterone is more specific than that of corticosterone. Serum concentration of testosterone and corticosterone tended to increase in comparison with the control on the 7th day after chronic treatment with morphine (0.5 mg/g food), when the urinary excretion of LMWP was significantly decreased. Furthermore, after rats were chronically administered morphine following castration or adrenalectomy, the urinary LMWP excretion was markedly decreased in the same way as found in intact animals. On the other hand, the serum thyroxine level of rats treated with morphine for 7 days was significantly lower than that of the control. Thyroxine increased dose-dependently the decreased urinary excretion of LMWP induced by morphine administration. These findings suggest that the decrease in urinary excretion of LMWP after chronic treatment with morphine may be caused by the change of serum thyroxine level via the action of morphine on the endocrine functions.

Adrenalectomy↗
PubMed1983

Urinary sex-dependent low molecular weight proteins as a sign of narcotic dependence in male rats.

The relationship between urinary excretion of sex-dependent low molecular weight proteins (LMWP) in male rats and narcotic dependence has been investigated in this study. Chronic administration of codeine (0.5 mg/g food) caused a significant decrease in urinary excretion of LMWP from the third day, without any change in urinary high molecular weight proteins. The decrease recovered to the control level after the withdrawal of codeine. Withdrawal symptoms including loss of body weight and diarrhea were observed following codeine withdrawal. In animals chronically treated with pethidine (1.0 mg/g food), however, neither changes in urinary LMWP excretion nor withdrawal symptoms were observed. These present findings suggest that the decrease in urinary excretion of sex-dependent LMWP is related to narcotic dependence in male rats, since we previously reported the decrease in urinary excreted LMWP in morphine-dependent rats.

Albuminuria↗
PubMed1982

[Plasma corticosterone concentration in morphine-dependent rats].

The effects of morphine on plasma corticosterone concentration in rats were studied using the drug-admixed food method. Morphine was mixed with the powder form of rat food in concentrations of 0.5 mg/g, 1 mg/g, and 2 mg/g of food. Plasma corticosterone concentration in rats treated with morphine-admixed food increased significantly, and the increment depended on the morphine concentration of drug-admixed food. The time course change of plasma corticosterone concentration in rats treated with morphine-admixed food (1 mg/g food) for 1 week was similar to that of non-treated rats without the concentration at 9:00. The plasma corticosterone concentration of morphine-treated rats at 9:00 was significantly increased in comparison with that of non-treated rats. Furthermore, the plasma corticosterone concentration after withdrawal in morphine-treated rats increased with time, and a significant increment in corticosterone was observed at 24 hr after the withdrawal. Naloxone, injected subcutaneously into morphine-dependent rats, significantly increased plasma corticosterone concentration. Increment of plasma corticosterone concentration in rats treated with morphine-admixed food for 3 or 4 weeks was significantly different from the non-treated group. The increment of plasma corticosterone concentration after the withdrawal was in a morphine treatment period-related manner. By these results, we suggest that tolerance to the increment action in plasma corticosterone concentration of morphine does not develop for at least 4 weeks using the drug-admixed food method, and the drug-admixed food method could induce morphine dependence without disturbance of the circadian rhythm in plasma corticosterone.

Animals↗
PubMedDate not supplied

Molecular distinction between muscarinic acetylcholine receptor subtypes.

The muscarinic acetylcholine receptor (mAChR) mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels, through the action of guanine nucleotide-binding regulatory proteins. Pharmacologically distinguishable forms of the mAChR occur in different tissues and have provisionally been classified into M1 (I), M2 cardiac (II) and M2 glandular (III) subtypes on the basis of their difference in apparent affinity for antagonists. In an attempt to elucidate the molecular basis of the functional heterogeneity of the mAChR, we have cloned and sequenced DNAs complementary to porcine cerebral and cardiac messenger RNAs encoding mAChRs and have thereby deduced the primary structures of the receptor proteins. We report here that the messenger RNA generated by transcription of the cardiac complementary DNA directs the formation of a functional mAChR in Xenopus oocytes and that this mAChR differs from the mAChR formed by expression of the cerebral cDNA both in acetylcholine (ACh)-induced response and in antagonist binding properties. Our results provide evidence indicating that the mAChR encoded by the cerebral cDNA (designated as mAChR I) and the mAChR encoded by the cardiac cDNA (mAChR II) are of the M1 (I) and the M2 cardiac (II) subtype, respectively.

Acetylcholine↗