Serotonin contracts the rat mesenteric artery by inhibiting 4-aminopyridine-sensitive Kv channels via the 5-HT2A receptor and Src tyrosine kinase

Serotonin (5-hydroxytryptamine (5-HT)) is a neurotransmitter that regulates a variety of functions in the nervous, gastrointestinal and cardiovascular systems. Despite such importance, 5-HT signaling pathways are not entirely clear. We demonstrated previously that 4-aminopyridine (4-AP)-sensitive voltage-gated K+ (Kv) channels determine the resting membrane potential of arterial smooth muscle cells and that the Kv channels are inhibited by 5-HT, which depolarizes the membranes. Therefore, we hypothesized that 5-HT contracts arteries by inhibiting Kv channels. Here we studied 5-HT signaling and the detailed role of Kv currents in rat mesenteric arteries using patch-clamp and isometric tension measurements. Our data showed that inhibiting 4-AP-sensitive Kv channels contracted arterial rings, whereas inhibiting Ca2+-activated K+, inward rectifier K+ and ATP-sensitive K+ channels had little effect on arterial contraction, indicating a central role of Kv channels in the regulation of resting arterial tone. 5-HT-induced arterial contraction decreased significantly in the presence of high KCl or the voltage-gated Ca2+ channel (VGCC) inhibitor nifedipine, indicating that membrane depolarization and the consequent activation of VGCCs mediate the 5-HT-induced vasoconstriction. The effects of 5-HT on Kv currents and arterial contraction were markedly prevented by the 5-HT2A receptor antagonists ketanserin and spiperone. Consistently, alpha-methyl 5-HT, a 5-HT2 receptor agonist, mimicked the 5-HT action on Kv channels. Pretreatment with a Src tyrosine kinase inhibitor, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine, prevented both the 5-HT-mediated vasoconstriction and Kv current inhibition. Our data suggest that 4-AP-sensitive Kv channels are the primary regulator of the resting tone in rat mesenteric arteries. 5-HT constricts the arteries by inhibiting Kv channels via the 5-HT2A receptor and Src tyrosine kinase pathway.

Nonpharmacologic Pain Relief with Oral 25% Dextrose or/and Pacifier for Newborn Infants

PURPOSE: The goal of this study was to compare the efficacy of oral 25% dextrose treatment or/and pacifier for analgesia in healthy newborns during intramuscular injection of a hepatitis B vaccine. METHODS: A prospective, randomized, partially blinded, clinical trial was performed in 132 healthy newborns. They were assigned randomly to 4 treatment groups: control group (2 mL distilled water), dextrose group (2 mL 25% dextrose), pacifier group, dextrose+ pacifier group (pacifier coating with 25% dextrose) during intramuscular injection of hepatitis B vaccine. For all groups, Neonatal Infant Pain Scale (NIPS), Neonatal Facial Coding System (NFCS), Premature Infant Pain Profile (PIPP) scores were evaluated before the injection, during the injection, and at 2 minutes after the injection. Pain scores were compared among the 4 groups. RESULTS: Maternal and neonatal characteristics were similar among the 4 groups. 25% dextrose treatment led to lower NIPS pain scores during injection (6.4+/-0.9 vs. 5.5+/-1.7, P=0.01) and after injection (1.6+/-2.0 vs. 0.6+/-0.9, P=0.01) and NFCS pain scores after injection (1.5+/-2.3 vs. 0.7+/-0.8, P=0.04) than control group. The number of neonates who feel the pain (indication of scores: NIPS> or =4, NFCS> or =3) decreased (9 (23.1%) vs. 0 (0%), P=0.04 via NIPS, 7 (17.9%) vs. 0 (0%), P=0.02 via NFCS). However, all treatment groups did not decreased PIPP scores, compared with the control group. CONCLUSION: Oral 25% dextrose is effective than distilled water or using pacifier with or without 25% dextrose in reducing pain during intramuscular injection of hepatitis B vaccinations. Further study based on this preliminary study need about nonpharmacologic management of pain in newborns.

Roles of Non-cholinergic Intrapancreatic Nerves, Serotonergic Nerves, on Pancreatic Exocrine Secretion in the Isolated Perfused Rat Pancreas

It has been rereported that axons which display 5-hydroxytryptamine (5-HT) immunoreactivity are abundant in the pancreas and the majority of serotonergic axons terminate within intrapancreatic ganglia, islet and acini. This histological result strongly suggests that intrapancreatic serotonergic nerves could affect to the pancreatic endocrine and exocrine secretion. Thus, this study was aimed to investigate whether intrapancreatic serotonergic nerves could affect pancreatic exocrine secretion and an action mechanism of the intrapancreatic serotonergic nerves. The rats were anesthetized with a single injection of urethane. The median line and the abdominal aorta was carefully dissected and cannulated with PE-50 tubing just above the celiac artery, and then tightly ligated just below the superior mesenteric artery. The pancreatic duct was also cannulated with Tygon microbore tubing. With the addition of serotonin, pancreatic volume flow and amylase output were significantly inhibited electrical field stimulation (EFS). On the other hand, pancreatic volume flow and amylase output were significantly elevated in EFS with the addition of spiperone. EFS application, however, pancreatic volume flow and amylase output had no significant change in cholecystokinin (CCK) alone when serotonin was applied under a 5.6 mM glucose background. Pancreatic volume flow and amylase output under 18 mM glucose background were significantly elevated in CCK plus serotonin than in CCK alone. These data suggest that intrapancreatic serotonergic nerves play an inhibitory role in pancreatic exocrine secretion and an important role in the insulin action or release.

Similarities and Differences between DSM-IV Brief Psychotic Disorder and ICD-10 Acute and Transient Psychotic Disorder / 신경정신의학

Time is the most important factor in defining the diagnostic concepts of DSM-IV brief psychotic disorder (BPD) and ICD-10 acute and transient psychotic disorder (ATPD). Time factor is more complicated in ICD-10 ATPD than in DSM-IV BPD because he first time factor in ICD-10 ATPD concerns the development of symptoms (acute onset within 2 weeks), and the second factor, the duration of an episode, depends on the subtypes of ICD-10 ATPD. For instance, the duration of an episode in acute polymorphic psychotic disorder (APPD) with symptoms of schizophrenia must not exceed I month, while APPD without symptoms of schizophrenia may occur forup to three months. Despite the differences with respect to time factor in DSM-IV BPD and ICD-10 ATPD, it is not necessary to consider them as separate diagnostic entitie because they are identical in almost all of the essential clinical parameters. The strict criterion of episode duration in DSM-IV BPD should therefore be reconsidered. The APPD within ICD-10 ATPD subtypes, which is very similar to both cycloid psychosis and bouffee delirante, has a significant diagnostic concordance with DSM-IV BPD, and can be distinguished more clearly from schizophrenia and bipolar schizoaffective disorder. In contrast, ASPD not only has similarities to schizophrenia but also to bipolar schizoaffective disorder. This means that ASPD could function as a bridge between one end of the psychotic continuum occupied by schizophrenia and the opposite end occupied by major affective disorder. Taking this into consideration, ICD-10 ATPD could be much more homogeneous if APPD was not combined with ASPD. On the other hand, the symptomatologic polymorphism carries the most relevant distinguishing power in differentiating the subtypes of ICD-10 ATPD, so the distinction of APPD with and without symptoms of schizophrenia is not needed.

The effect of sucrose on infants during a painful procedure / 소아과

PURPOSE: The purpose of this study was to test the efficacy of treating the pain among newborn infants associated with a medical procedure with sucrose with regard to overall physiological and behavioral stability. METHODS: 103 newborn infants were enrolled in this study. The control group (n=63) did not receive any treatment. The experimental group (n=40) received 2 mL of 24% sucrose solution two minutes before a routine heel stick. The pain was assessed by measurements of physiological changes [e.g. pulse rate, oxygen saturation, salivary cortisol (hydrocortisone)] and behavioral changes [e.g. crying time, and the neonatal infant pain scale (NIPS) for neonates]. RESULTS: There were no differences among the groups with respect to physiological changes associated with the pain from the procedure. However, there were significant group differences in behavioral changes to the pain. In the control group, the median crying time was 13 seconds, while in the experimental group, the median crying time was 3.5 seconds (P=.000). In the control group the median NIPS score was 4, while in the experimental group the median NIPS score was 2 (P=.000). CONCLUSIONS: These findings suggest that sucrose can be an effective method for the management of stress responses in infants with regard to behavior. However, this treatment had no significant physiological effects.

Induction of ovarian growth in Aegla platensis (Crustacea, Aeglidae) by means of neuroregulators incorporated to food

The freshwater crab Aegla platensis was used as a model to induce ovarian growth by adding different neuroregulators to a pellet food formulation. Added compounds were the dopaminergic inhibitor spiperone or the enkephalinergic inhibitor naloxone, both of them at a dose of 10-8 mol/animal. Animals were fed on the enriched pellets twice a week. After 7 wk, the gonadosomatic index (GI) was calculated as (gonad fresh weight / body fresh weight) x 100. GI significantly increased only for those females fed on spiperone pellets, compared to a control group receiving pellets with no compound added. During the assayed period, spiperone would be reverting the arrest exerted by dopamine on the neuroendocrine stimulation of ovarian growth. On the other hand, for both spiperone and naloxone a higher GI was correlated to a higher lipid content of both gonads and/or hepatopancreas, suggesting an increased energetic demand in accordance with an active investment in reproduction. Rev. Biol. Trop. 56 (3): 1201-1207. Epub 2008 September 30.

Se utilizó al anomuro de agua dulce Aegla platensis como modelo para inducir el crecimiento ovárico mediante el agregado de diferentes neuroreguladores a una formulación de alimento pelleteado. Los compuestos agregados fueron el inhibidor dopaminergico spiperona ó el inhibidor encefalinérgico naloxone, ambos a una dosis de 10-8 moles/animal. Los animales fueron alimentados dos veces a la semana con pellets enriquecidos con alguno de los neuroreguladores. Luego de 7 semanas, se calculó el índice gonadomático (IG) como (peso gonadal fresco/ peso corporal fresco) x 100. El IG mostró un incremento significativamente sólo en aquellas hembras alimentadas con pellets enriquecidos con spiperona, en comparación con un grupo control que recibió pellets sin agregado alguno. Durante el período ensayado, la spiperona estaría revirtiendo el arresto ejercido por la dopamina sobre la estimulación neuroendocrina del crecimiento ovárico. Por otro lado, para ambos grupos experimentales (spiperona y naloxone), un mayor valor de IG estuvo correlacionado a un mayor incremento del contenido de lípidos tanto en gonadas como en hepatopáncreas, sugiriendo una demanda energética incrementada en relación con una activa inversión en reproducción.

N-( 4- 18F Fluoromethylbenzyl ) spiperone: A Selective Radiotracer for In Vivo Studies of Dopamine D2 Receptors / 대한핵의학회잡지

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[F] fluorornethylbenzyl)spiperone ([F]FMBS), a newly developed derivative of spiperone, as a potentially more selective #radiotrar.er for the dopamine (DA) Dz receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [F]FMBS by tail vein injectivn. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA Dp receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA Dr lSCH 23390), DA transporter (GBR 12909), and serotonin Sp (5-HTz) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabe1ed FMBS (1 rng/kg) and spiperone (1 mg/kg) reduced [F] FMBS striatal-to-cerebellar ratio by 41Zo and 80Ya, respectively. (+)-Butaclamol(1 mg/kg) blocked 80Yo of the striatal [F]FMBS binding, while (-)-butaclamol (1 rng/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect. On [""F]FMBS binding. Ketanserin (1 mg/kg), a ligand for the 5-H1g receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [F]FMEtS labels DA Dz receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA Dz receptors in vivo by PET.

Daily variation in plasma concentration of fencamfamine and striatal dopamine receptors in rats

Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection at 21:00 h. Moreover, at 15:00, 21:00 and 03:00 h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [3H]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation, a phenomenon that should be considered to explain the circadian time-dependent effects of FCF

Modulation of feeding and drinking by dopamine in caudate and accumbens nuclei in rats.

Injection of dopamine (DA) into accumbens and caudate nuclei facilitates a dose-dependent increase in food and water intake, whereas administration of spiperone (SP), a central D2-receptor antagonist suppresses DA-facilitated food and water intake. Bilateral lesions of nucleus accumbens and caudatus result in a sustained and significant decrease in food and water intake. The results suggest that DA is a neurotransmitter involved in feeding and drinking behavior in accumbens and caudate nuclei and this effect is mediated by central D2 receptors.

Propiedades antiadrenérgicas alfa de la espiroxatrina, un ligando de los receptores serotonérgicos 5-HT1A / Antiadrenergic properties of spiroxatrine

La espiroxatrina, un ligando 5-HT1A, tiene muy baja afinidad por los sitios de unión Ó1-adrenérgicos y una afinidad relativamente alta por los sitios Ó2. No obstante, estudios funcionales recientes indican que la espiroxatrina es un potente antagonista de los receptores adrenérgicos a1 que median la contracción de la aorta de rata in vitro. Tomando en consideración las notables diferencias en la interacción de los fármacos con los receptores adrenérgicos Ó presentes en los diferentes modelos experimentales, el presente estudio fue diseñado para analizar las propiedades antagonistas Ó-adrenérgicas de la espiroxatrina en la rata descerebrada y desmedulada montada para el registro de la presión arterial. La norepinefrina y los agonistas adrenérgicos Ó1 y Ó2 metoxamina y clonidina, respectivamente, produjeron incrementos de la presión arterial en forma dependiente de la dosis. La espiroxitrina (1 mg/kg, i.v.) produjo un desplazamiento significativo de las curvas dosis-respuesta a los tres agonistas. La magnitud de dicho desplazamiento fue similar en los tres casos. Los resultados presentes sugieren que, aunque la espiroxatrina presenta propiedades antiadrenérgicas Ó1 y Ó2 en el modelo in vivo utilizado en este estudio, su potencia antagonista no parece corresponder con la encontrada en la aorta de rata. La posible participación de subtipo del receptor adrenérgico Ó1 es discutida

Septal polydipsia in rats is a primary polydipsia not mediated by dopamine.

Bilateral lesions of nucleus septal lateralis resulted in a sustained and significant increase in water intake, without any change in food intake. Intracerebral injection of dopamine (DA) or of spiperone (a central D2-receptor antagonist) did not elicit any change in water or food intake. The polydipsia resulting from septal lesions is thus a primary polydipsia, which is independent of food intake, and is not mediated by neurotransmitter dopamine.