[Metabotropic glutamate receptors: new molecular targets in the treatment of neurological and psychiatric diseases]. / Receptores metabotrópicos de glutamato: nuevas dianas moleculares en la terapia de enfermedades neurológicas y psiquiátricas.

AIM: To describe the current state of knowledge about the processes of neuronal signalling mediated by the metabotropic glutamate (mGlu) receptors and their potential role in the treatment of neurological and psychiatric disorders. DEVELOPMENT: The mGlu receptors are a large family of G-protein coupled receptors that modulate excitatory synaptic transmission through several transduction mechanisms. Recent advances in the molecular biology, physiology and pharmacology of these receptors revealed their potential role in a variety of central nervous system disorders such as epilepsy, pain, ischemia, and neurodegenerative diseases. These findings have shown that modulating glutamatergic transmission with drugs interacting selectively on mGlu receptors might have important beneficial effects. A number of results in this direction are very promising and are used to develop new drugs that overcome the multiple side-effects produced by the drugs acting on ionotropic glutamate receptors. Thus, several evidence have provided clear indications of the potential use of selective agonists and antagonists of the different mGlu receptor subtypes as neuroprotective agents. CONCLUSIONS: Determining the role of mGlu receptors in physiological as well as in pathophysiological states will be relevant to develop new treatments for diseases in which glutamatergic neurotransmission is altered. In this sense, the current progress indicates that mGlu receptors are novel and promising therapeutic targets for neurological and psychiatric disorders.

Receptores metabotrópicos de glutamato: nuevas dianas moleculares en la terapia de enfermedades neurológicas y psiquiátricas / Metabotropic glutamate receptors: new molecular targets in the treatment of neurological and psychiatric diseases

Objetivo. Describir el estado actual de conocimientos sobre los procesos de señalización neuronal mediados por los receptores metabotrópicos de glutamato (mGlu) y su potencial papel en el tratamiento de enfermedades neurológicas y psiquiátricas. Desarrollo. Los receptores mGlu son una gran familia de receptores acoplados a proteínas G que modulan la transmisión sináptica excitadora a través de varias vías de transducción. Las investigaciones centradas en conocer la biología molecular, fisiología y farmacología de los receptores mGlu han puesto de manifiesto su implicación en varios trastornos del sistema nervioso central, entre los que destacan la epilepsia, el dolor, la isquemia y las enfermedades neurodegenerativas. Estos descubrimientos han permitido demostrar que la modulación de la transmisión glutamatérgica con fármacos que actúan selectivamente sobre los receptores mGlu puede tener importantes efectos beneficiosos. Los resultados obtenidos son muy prometedores y están siendo aprovechados para el desarrollo de nuevos medicamentos que han permitido solucionar los múltiples efectos secundarios producidos por los fármacos que actúan sobre los receptores ionotrópicos de glutamato. En esta dirección, existen claras evidencias del uso potencial de agonistas y antagonistas selectivos de los distintos tipos de receptores mGlu como agentes neuroprotectores. Conclusiones. Determinar el papel de los receptores mGlu en condiciones fisiológicas y patológicas es de especial relevancia para el desarrollo de nuevos tratamientos de enfermedades producidas por alteraciones en la neurotransmisión glutamatérgica. En este sentido, los progresos actuales indican que los receptores mGlu constituyen nuevas y prometedoras dianas para la terapia de enfermedades neurológicas y psiquiátricas

Aim. To describe the current state of knowledge about the processes of neuronal signalling mediated by the metabotropic glutamate (mGlu) receptors and their potential role in the treatment of neurological and psychiatric disorders. Development. The mGlu receptors are a large family of G-protein coupled receptors that modulate excitatory synaptic transmission through several transduction mechanisms. Recent advances in the molecular biology, physiology and pharmacology of these receptors revealed their potential role in a variety of central nervous system disorders such as epilepsy, pain, ischemia, and neurodegenerative diseases. These findings have shown that modulating glutamatergic transmission with drugs interacting selectively on mGlu receptors might have important beneficial effects. A number of results in this direction are very promising and are used to develop new drugs that overcome the multiple side-effects produced by the drugs acting on ionotropic glutamate receptors. Thus, several evidence have provided clear indications of the potential use of selective agonists and antagonists of the different mGlu receptor subtypes as neuroprotective agents. Conclusions. Determining the role of mGlu receptors in physiological as well as in pathophysiological states will be relevant to develop new treatments for diseases in which glutamatergic neurotransmission is altered. In this sense, the current progress indicates that mGlu receptors are novel and promising therapeutic targets for neurological and psychiatric disorders

Neurons expressing 5-HT2 receptors in the rat brain: neurochemical identification of cell types by immunocytochemistry.

The serotonin2 (5-HT2) receptor has been implicated in a number of behavioral and physiological processes. It may also play a role in cellular development and differentiation, and represents a site of action of hallucinogens and certain psychotherapeutic drugs. To better understand the functions and regulation of the 5-HT2 receptor, we have undertaken a series of studies in which we attempted to identify the specific cell types that express the receptor. This was accomplished using a variety of double-labeling strategies with an antibody we raised against the rat 5-HT2 receptor protein. In this review, we recount of some of our previously published findings and present some new data in which we identify subpopulations of cholinergic neurons in the brainstem and gamma-aminobutynic acid (GABA)ergic interneurons in the cortex that express 5-HT2 receptor immunoreactivity. Developmentally, the appearance of 5-HT2 receptor immunoreactivity occurs relatively late in teh ontogeny of the cells in which it is expressed, mostly in the early postnatal period. This argues against a significant role for this receptor in early development, though it may participate in some aspect of terminal differentiation. We discuss the significance of the cell-type-specific and temporal expression of the 5-HT2 receptor in the context of current hypotheses of neuropsychiatric disorders such as schizophrenia.

Stereological study of the synaptic profiles belonging to interneurons in the dorsal lateral geniculate nucleus of the rabbit.

This study is concerned with some characteristics of the interneurons belonging to the dLGN (dorsal Lateral Geniculate Nucleus) of the rabbit. The work deals with the distribution of such cells in the alpha E sector of the nucleus and their F1 and F2 presynaptic contacts. The F1 and the F2 profiles are present in all three of the alpha E zones studied. The F1 profiles are significantly more numerous in the upper zone (57 +/- 2 profiles per 10(4) microns2 of section) and the middle zone (59 +/- 3 profiles per 10(4) microns2 of section) than in the lower one (41 +/- 2 profiles per 10(4) microns2 of section). The F2 profiles are more abundant in the alpha E sector than the F1 ones are, particularly in the lower zone, where F2 profiles (104 +/- 4 profiles per 10(4) microns2 of section) are not only significantly more numerous than F1 profiles but also more abundant than the F2 profiles in the middle zone (84 +/- 3 profiles per 10(4) microns2 of section) and upper zone (88 +/- 2 profiles per 10(4) microns2 of section). These results and their comments reveal diverse density of the element distribution from the dorsal to the ventral part of the alpha E sector as well as the possible relationship or independence from the extranuclear afferent inputs.