The site of action for the sleep-promoting effect of prostaglandin (PG) D2 was extensively examined in the brain of adult male rats (n = 231). PGD2 was administered at 100 pmol/0.2 pI per min for 6 hr (2300-0500 hr) through chronically implanted microdialysis probes or infusion cannulae. Among the administrations of PGD2 by dialysis probes (n = 176), only those (n = 8) to a ventro-rostral part of the basal forebrain by the probes implanted on the midline consistently increased slow-wave sleep (SWS), by 51 ± 6 min (mean ± SEM) above the baseline value (111 ± 11 min). Since this area is separated by a cleft into right and left regions, the results were interpreted to mean that, through this cleft, PGD2 diffused in the subarachnoid space over the adjacent ventral surface, where it had the effect ofpromoting sleep. When PGD2 was directly infused into the subarachnoid space (n = 55), extraordinary increases exceeding 90 min were consistently attained for the SWS at sites located between 0.5 and 2 mm rostral to the bregma and between 0 and 1.2 mm lateral to the midline defined according to the stereotaxic coordinates adopted from the brain atlas of Paxinos and Watson [Paxinos, G. & Watson, C. (1986) The Rat Brain in Stereotaxic Coordinates (Academic, San Diego)]. Thus, we demarcated a "PGD2-sensitive, sleep-promoting zone" within this region in the ventral surface of the rostral basal forebrain. During the bilateral infusion of PGD2 into the subarachnoid space of this zone, the hourly mean SWS level of the nocturnal animals (n = 6) in the night reached the maximum at the second hour of the infusion period; this maximum hourly SWS level, corresponding to the daytime level of the same animals, lasted until the end of PGD2 infusion.Prostaglandin D2 (PGD2) has been postulated as one of the endogenous sleep-promoting substances in rats and other mammals including humans (1). PGD2 has been implicated in the physiological regulation of sleep by the fact that sleep in rats was markedly suppressed by intracerebroventricular (2) or intravenous (3) administration of inorganic selenium compounds, which are inhibitors of PGD synthase (EC 5.3.99.2), the enzyme responsible for the synthesis of PGD2 in the rat brain (4).The preoptic area (POA) has long been proposed as a sleep center since the experimental study by Nauta in 1946 (5). The site of action for the sleep-promoting effect of PGD2 has been postulated to be located in or near the POA since an increase in the amount of sleep was first demonstrated with PGD2 in 1982 by a microinjection study (6). Subsequent studies in monkeys (7) and rats (8) also supported the assumption that the site of action is located in a rostral and ventral region, adjacent to the third cerebral ventricle; however, the exact site of action has not yet been clearly defined.In this paper, the site most effective in promoting sleep with PGD2 administration was extensively studied by use of the microdialysis technique and the continuous infusion method. The results clearly define the site of action ...

The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.Hypnogenic effects of adenosine were shown by its intracerebroventricular administration in fowls (4) and dogs (5). Subsequently, the effects of adenosine and its analogues on sleep-wake activities were studied in rats by . Recently, Rainnie et al. (10) suggested the cholinergic neurons of the mesopontine tegmentum and in the diagonal band of Broca as the target site of adenosine for sleep promotion in vitro. These studies suggested that the A1-adenosine receptor may be involved in the regulation of sleep. On the other hand, the role of A2a-adenosine receptor on behavior had focused on the locomotor depression (11-13) and had not been linked to the sleep-wake phenomena.In the current study, we demonstrated that stimulation of A2-adenosine receptors located in the rostral basal forebrain caused a marked increase in sleep. We also showed that this receptor subtype plays a crucial role in the sleep-promoting mechanism triggered by PGD2.

Cell motility is an important cellular function closely related to the processes of tumour progression and metastasis. Several members of transmembrane 4 superfamily (TM4SF) have been reported to be associated with cell motility and metastatic potential of solid tumour. The aim of this study is to clarify the clinical significance of the member of TM4SF (MRP-1/CD9, KAI1/CD82 and CD151) in human colon cancer. We studied 146 colon cancer patients who underwent curative surgery and studied the expression of MRP-1/ CD9, KAI1/CD82 and CD151 using reverse transcriptase -polymerase chain reaction and immunohistochemistry. We found that 64 patients (43.8%) had MRP-1/CD9-positive tumours and that the overall survival rate of patients with MRP-1/CD9-positive tumours was much higher than that of patients with MRP-1/CD9-negative tumours (89.8 vs 50.8%, Po0.001). In contrast, 63 patients (43.2%) had KAI1/CD82-positive tumours and the overall survival rate of patients with KAI1/CD82-positive tumours was also higher than that of patients with KAI1/CD82-negative tumours (84.8 vs 54.9%, P ¼ 0.002). On the other hand, positive CD151 expression had a bad effect on the overall survival rate of patients with colon cancer (61.2 vs 74.9%, P ¼ 0.022). In a multivariate analysis, MRP-1/CD9 status was a good indicator of the overall survival (P ¼ 0.007). We have shown that the reduction of MRP-1/CD9 and KAI1/CD82 expression, and the increasing CD151 expression are indicators for a poor prognosis in patients with colon cancer. This is a first report describing about the relation between CD151 and colon cancer.

The study confirmed reduced CSF histamine levels in hypocretin-deficient narcolepsy with cataplexy. Similar degrees of reduction were also observed in hypocretin non-deficient narcolepsy and in idiopathic hypersomnia, while those in OSAS (non central nervous system hypersomnia) were not altered. The decrease in histamine in these subjects were more specifically observed in non-medicated subjects, suggesting CSF histamine is a biomarker reflecting the degree of hypersomnia of central origin.

The present study has demonstrated that the sleep-promoting potency of 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS21680), a selective agonist for the adenosine A2A receptor, varies depending on the location of the administration. CGS21680 was continuously administered to rats through a chronically implanted cannula for 6 h during their active phase. The tip of the cannula was located in the subarachnoid space or the brain ventricle neighbouring the established brain areas implicated in the regulation of sleep-wake phenomena, i.e. rostral basal forebrain, medial preoptic area, lateral preoptic area, posterior hypothalamus, and dorsal tegmentum of the pons and medulla. At an infusion rate of 2.0 pmol/min, the magnitude of increase in non-rapid eye movement sleep varied from 14 min (a 15% increase) to 96 min (a 103% increase), and those of rapid eye movement sleep varied from 6 min (a 40% increase) to 28 min (a 264% increase) from the respective baseline values. The largest increases in both types of sleep occurred when CGS21680 was administered to the subarachnoid space underlying the rostral basal forebrain. These findings were interpreted to mean that the major, if not the only, site responsible for the CGS21680-inducing sleep was located in or near the rostral basal forebrain. This interpretation was supported by the findings that the administration of CGS21680 to the rostral basal forebrain produced predominant expression of Fos within the shell of the nucleus accumbens and the medial portion of the olfactory tubercle, and that the microdialysis perfusion of CGS21680 into the shell of the nucleus accumbens also exhibited a sleep-promoting effect.