The classical 'hypnotoxin theory' was followed by extensive search for an endogenous sleep substance. Brain tissues and body fluids of sleeping and sleep-deprived animals contained active sleep-inducing factors like the sleep-promoting substance (SPS). Uridine and oxidized glutathione (GSSG), two components of SPS, seem to regulate physiological sleep differentially. Uridine may facilitate the inhibitory neurotransmission at the synaptic level of the GABAA-uridine receptor complex. In contrast, GSSG may inhibit the excitatory neurotransmission at the synaptic level of the glutamate receptor. Thus, the two SPS components promote sleep by exerting a complementary action on the two major neurotransmitter systems in the brain that have mutually reciprocal functions. Further, among multidimensional functions of sleep, uridine may contribute to recover the activity of neurons, while glutathione may counteract excitotoxic events. Hence sleep at the behavioral level is a process of neuronal restitution and detoxification at the cellular level. Such a concept can be regarded as a modern version of the Ishimori-Piéron's hypnotoxin theory proposed early in this century.

Animals↗

PubMedDate not supplied

A method for measurement of muscarinic receptor-mediated responses in dissociated single colon longitudinal smooth muscle cells.

We previously reported a simple method of acutely preparing dissociated smooth muscle cells from urinary bladder tissue, but the feasibility of this method has not been well ascertained. In the present study, we assessed whether this method is applicable for measuring muscarinic receptor function in intestinal smooth muscle cells. Single smooth muscle cells were prepared from the longitudinal muscle tissue of guinea pig colon by the enzymatic dissociation with papain and hyaluronidase, followed by collagenase digestion. Muscarinic responses in the isolated smooth muscle cells were measured by intracellular Ca(2+) mobilization and extracellular acidification through Fura-2 fluorometry and Cytosensor microphysiometry, respectively. A single, viable population of colon longitudinal smooth muscle cells (approximately 6 x 10(6) cells/animal) was obtained. In these cells, carbachol (muscarinic agonist) induced Ca(2+) mobilization and extracellular acidification over the concentration range similar to that previously reported to produce contraction of the intact colon muscle strips. Atropine (nonselective muscarinic antagonist) and 4-diphenylacetoxy-N-methylpiperidine (4-DAMP, M(3)-selective antagonist) inhibited the Ca(2+) mobilization with potencies approximately 3 log units greater than that for methoctramine (M(2)-selective antagonist). For extracellular acidification, the potency differences between these antagonists was approximately 2 log units. In addition, the carbachol-induced extracellular acidification was inhibited by 5-[N-ethyl-N-isopropyl]-amiloride, a selective inhibitor of the Na(+)/H(+) exchanger. These findings indicate that in isolated colonic smooth muscle cells, M(3) receptors are predominantly involved in Ca(2+) mobilization, while a mixed population of M(2) and M(3) receptors seems to contribute to extracellular acidification. Our results further suggest the role of the Na(+)/H(+) exchanger in muscarinic-mediated extracellular acidification. Consequently, our method produces viable isolated colonic smooth muscle cells that display physiologically appropriate responses to muscarinic receptor activation, and the method may be applicable for several types of nonvascular smooth muscle tissues.

Amiloride↗

PubMedDate not supplied

Peyer's patch organogenesis as a programmed inflammation: a hypothetical model.

Gene-knock-out studies implicate roles of lymphotoxin (LT) alphabeta and LT betaR in the initial phase of Peyer's patch (PP) organogenesis. We recently identified the requirement of IL-7R alpha/gamma c/Jak3 signal in LT alphabeta production of IL-7R alpha+ cells. These observations lead us to a hypothetical model for PP organogenesis with three cellular components. The first is the producer of the ligand for IL-7R alpha, which then stimulate the IL-7R alpha+ cells to produce LT alphabeta activating the LT betaR+ cells to form an organizing center for PP organogenesis. This model is similar to that of inflammation, suggesting that PP organogenesis is a programmed version of inflammation.

Animals↗

PubMedDate not supplied

Brain death in Japan.

Explore the source record for details and available documents.

Death↗

PubMedDate not supplied

Pharmacological profile of orally administered YM087, a vasopressin antagonist, in conscious rats.

1. YM087 is a newly synthesized non-peptide arginine vasopressin (AVP) antagonist that shows high affinity for both V1A and V2 receptors. In the present study, the V1A and V2 receptor antagonist effects of orally administered YM087 were assessed in conscious rats. 2. In conscious rats, orally administered YM087 (0.1, 0.3 and 1.0 mg/kg) did not affect basal blood pressure, but YM087 dose-dependently inhibited 30 mU/kg, i.v., AVP-induced pressor responses. This inhibition lasted for over 8 h following the oral administration of the highest dose of YM087 (1 mg/kg). 3. In rats deprived of water and food for 16-18 h, oral administration of YM087 (0.1, 0.3, 1 and 3 mg/kg) dose-dependently increased urine volume and reduced urine osmolality, with associated increases in urinary sodium and potassium excretion. However, these increases in electrolyte excretion were lower than those seen at comparable diuretic doses of furosemide (3, 10, 30 and 100 mg/kg, p.o.). 4. Oral administration of YM087 (0.3, 1 and 3 mg/kg) produced a dose-dependent increase in urine volume in rats allowed free access to water, with the diuretic effect peaking 2-4 h post-dosing at all dose levels. The diuretic effect of YM087 was sustained 8-10 h after a dose of 3 mg/kg; this is in contrast with the transient diuresis seen after furosemide (100 mg/kg, p.o.) dosing. 5. The present results demonstrate that YM087 is an orally active AVP antagonist with potent and long-lasting effects. YM087 suppressed V1A receptor-mediated pressor responses to AVP with minimal effects on basal haemodynamics and exerted a diuretic effect without increased electrolyte excretion by inhibiting V2 receptor-mediated water reabsorption.

Administration, Oral↗

PubMedDate not supplied

Removal of immunosuppressive substance in cancer patients' serum.

Anemia-inducing substance (AIS) appears in plasma as cancer progresses. In this study, a non-coated charcoal column was used to remove AIS from the cachectic plasma obtained from patients with advanced cancer. AIS could be completely removed by 6 cycles of adsorption using this column. Similar data were obtained in an experiment using VX-2-transplanted rabbits. These observations raised the possibility that plasmapheresis with a non-coated charcoal column may be available as a new means of immunotherapy for advanced cancer.

Biological Factors↗