Succinate receptor GPR91, a Gαi coupled receptor that increases intracellular calcium concentrations through PLCβ

AbstractSuccinate has been reported as the endogenous ligand for GPR91. In this study, succinate was confirmed to activate GPR91 resulting in both 3′–5′-cyclic adenosine monophosphate (cAMP) inhibition and inositol phosphate formation in a pertussis toxin (PTX)-sensitive manner. GPR91 agonist-mediated effects detected using dynamic mass redistribution (DMR) were inhibited with PTX, edelfosine and U73122 demonstrating the importance of not only the Gαi pathway but also PLCβ. These results show that GPR91 when expressed in HEK293s cells couples exclusively through the Gαi pathway and acts through Gαi not only to inhibit cAMP production but also to increase intracellular Ca2+ in an inositol phosphate dependent mechanism via PLCβ activation

Pharmacological profiling of the hemodynamic effects of cannabinoid ligands: a combined in vitro and in vivo approach.

The receptors mediating the hemodynamic responses to cannabinoids are not clearly defined due to the multifarious pharmacology of many commonly used cannabinoid ligands. While both CB1 and TRPV1 receptors are implicated, G protein-coupled receptor 55 (GPR55) may also mediate some of the hemodynamic effects of several atypical cannabinoid ligands. The present studies attempted to unravel the pharmacology underlying the in vivo hemodynamic responses to ACEA (CB1 agonist), O-1602 (GPR55 agonist), AM251 (CB1 antagonist), and cannabidiol (CBD; GPR55 antagonist). Agonist and antagonist profiles of each ligand were determined by ligand-induced GTPcS binding in membrane preparations expressing rat and mouse CB1 and GPR55 receptors. Blood pressure responses to ACEA and O-1602 were recorded in anesthetized and conscious mice (wild type, CB1 / and GPR55 / ) and rats in the absence and presence of AM251 and CBD. ACEA demonstrated GTPcS activation at both receptors, while O-1602 only activated GPR55. AM251 exhibited antagonist activity at CB1 and agonist activity at GPR55, while CBD demonstrated selective antagonist activity at GPR55. The depressor response to ACEA was blocked by AM251 and attenuated by CBD, while O-1602 did not induce a depressor response. AM251 caused a depressor response that was absent in GPR55 / mice but enhanced by CBD, while CBD caused a small vasodepressor response that persisted in GPR55 / mice. Our findings show that assessment of the pharmacological profile of receptor activation by cannabinoid ligands in in vitro studies alongside in vivo functional studies is essential to understand the role of cannabinoids in hemodynamic control

Boganmeldelser

Book review

Seasonal depth distribution and thermal experience of the non-indigenous round goby Neogobius melanostomus in the Baltic Sea: implications to key trophic relations

Native to the Ponto-Caspian region, the benthic round goby (Neogobius melanostomus) has invaded several European inland waterbodies as well as the North American Great Lakes and the Baltic Sea. The species is capable of reaching very high densities in the invaded ecosystems, with not only evidence for significant food-web effects on the native biota and habitats, but also negative implications to coastal fishers. Although generally considered a coastal species, it has been shown that round goby migrate to deeper areas of the Great Lakes and other inland lakes during the cold season. Such seasonal movements may create new spatio-temporal ecosystem consequences in invaded systems. To seek evidence for seasonal depth distribution in coastal marine habitats, we compiled all available catch data for round goby in the Baltic Sea since its invasion and until 2017. We furthermore related the depths at capture for each season with the ambient thermal environment. The round goby spend autumn and winter at significantly deeper and offshore areas compared to spring and summer months; few fish were captured at depths 25 m. The thermal conditions at which round goby were caught varied significantly between seasons, being on average 18.3 °C during summer, and dropping to a low 3.8 °C during winter months. Overall, the fish sought the depths within each season with the highest possible temperatures. The spatial distribution of the round goby substantially overlaps with that of its main and preferred prey (mussels) and with that of its competitor for food (flatfish), but only moderately with the coastal predatory fish (perch), indicating thereby very complex trophic interactions associated with this invasion. Further investigations should aim at quantifying the food web consequences and coupling effects between different habitats related to seasonal migrations of the round goby, both in terms of the species as a competitor, predator and prey

Evaluación de la satisfacción y conocimientos en la rehabilitación del ictus tras la aplicación de medidas sistematicas de información, formación y soporte para pacientes y cuidadores

El ictus afecta abruptamente muchos aspectos de la vida del paciente superviviente y de sus familiares más cercanos. Su incidencia y el coste económico relacionado con la discapacidad secundaria van en aumento en la mayoría de países occidentales y en todo el mundo. El desarrollo de iniciativas que proporcionen de forma adecuada información sobre el ictus y su prevención, así como la formación necesaria para la adquisición de habilidades de auto-cuidado o manejo de estos pacientes, es clave para que una organización con recursos sanitarios limitados de respuesta a una sociedad que cada vez precisa con mayor nitidez una red socio-sanitaria integrada. La información precisa convierte a los pacientes y cuidadores en agentes activos con una mayor implicación en su proceso terapéutico, al mismo tiempo que reduce la incertidumbre y el miedo característicos después de un ictus. La formación del paciente y su cuidador en técnicas de auto-cuidado garantiza la máxima autonomía posible del paciente en su vida diaria, objetivo primordial del programa rehabilitador. A su vez, el soporte que desde las unidades de rehabilitación se proporcione al paciente con ictus y su familia es clave para reducir la soledad y aumentar los niveles de confianza y participación en la vida familiar o social de ambos. La satisfacción del paciente y cuidador con según qué aspectos del programa rehabilitador nos da información sobre si estamos respondiendo adecuadamente a sus necesidades más inmediatas después del ictus, y puede orientar al proveedor del servicio en cuanto a la organización del mismo. El aumento del nivel de conocimiento sobre el ictus del paciente y el cuidador, por otra parte, indica también que la medida educacional implantada está siendo eficaz. En este trabajo se evalúa la eficacia de una medida específica dirigida a proporcionar información, formación y soporte al paciente y su cuidador después del ictus. El aumento de la satisfacción de ambos, así como su nivel de conocimientos sobre esta afección demuestra que estas medidas son factibles y pueden ayudar en la adaptación de los pacientes y sus cuidadores en la nueva situación. Por otra parte, constatamos la necesidad de desarrollar en nuestro medio herramientas válidas que nos permitan evaluar los resultados de las intervenciones, ya sea en términos de satisfacción, conocimientos u otras variables de resultado. Por ello, se ha validado la versión en castellano de la Escala de Satisfacción de Pound, una herramienta específica, y con una gran aceptación internacional, para medir el grado de satisfacción del paciente con el programa rehabilitador seguido después del ictus. En base a nuestros resultados concluimos que la implantación sistemática de medidas dirigidas a la educación, formación y soporte de pacientes y cuidadores en el programa de rehabilitación seguido tras el ictus es factible y efectiva, y que la Escala de Satisfacción de Pound es una herramienta válida también en nuestro medio para medir la satisfacción con el programa rehabilitador seguido tras el ictus.Stroke abruptly affects many aspects of life of the surviving patients and their closest relatives. Incidence and the economic cost associated with secondary disability are increasing in most western countries and around the world. The development of initiatives that adequately provide information on stroke and its prevention, as well as the necessary training to acquire skills for self-care or management of these patients, is a key aspect for a care organization with limited health resources to respond to a society that increasingly needs, with greater clarity, an integrated socio-health network. Accurate information makes patients and caregivers in active agents with a greater involvement in their therapeutic process, while reduces uncertainty and fear, both characteristics after stroke. Patient education and caregiver training in self-care techniques ensures the maximum possible patient autonomy in their life, which is a primary objective in the rehabilitation program. Also support provided from stroke rehabilitation units for patients and their families is key to reduce their feelings of loneliness and increase levels of confidence and participation in family and social life. Patient and caregiver satisfaction with some aspect of the rehabilitation program gives us information about whether we are properly responding to their immediate needs after stroke, and can guide the service provider in terms of organization. The improvement in patients and caregivers' knowledge about stroke also may indicate that the educational measure is being implemented effectively. In this work we evaluate the efficacy of a specific measure to provide education, training and support for patients and caregivers after stroke. Increased levels of satisfaction, as well as the improvement of their knowledge about this condition shows this kind of measures are feasible and can help patients and caregivers adapt to the new situation. On the other hand, we note the need to develop valid tools that allow us to evaluate the results of new interventions, in terms of satisfaction, knowledge or other outcome variables. Therefore, we validate the spanish version of The Satisfaction Pound Scale, a specific tool and with a great international acceptance, to measure patient's satisfaction with the rehabilitation program after stroke. With this work we conclude that implementation of systematic measures for education, training and support for patients and caregivers in the rehabilitation program after stroke is feasible and effective, and that de Satisfaction Pound Scale is a valid tool also in our environment to evaluate patient satisfaction with the rehabilitation program after stroke