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Brain nitric oxide and ingestive behaviour
207
Pharmacological Research, Vol. 26, Supplement I, 1992 BRAIN NITRIC
OXIDE AND INGESTIVE BEHAVIOUR
F. Syuadrito. Institute of Pharmacology, ITALY.
School
of Medicine,
University
of Messina,
Nitric oxide (NO) synthase has been found in the brain. However the biological significance of NO presence in the Central Nervous System (CNS) has not been fully understood. We investigated its i volvement in drinking and feeding behaviour. Feedins behaviour: 8 an inhibitor of NO synthase, N -nitro-L-arginine (L-NO Arg), inhibited food intake in food deprived rats in a dose dependent manner. This effect was reverted by the administration of LFurthermore the administration of arginine (the NO precursor). L-NO Arg increased serotonin (5-HT) utilization in several brain .areas. In addition L-NO Arg suppressing effects on food intake were abated by a pretreatment with metergoline but not with ritanserin. Brain NO may therefore modulate 5-HT during feeding L-arginine inhibited, in a dosebehaviour. Drinkina behaviour: dependent manner,. water intake induced by water deprivation or by CNS administered angiotensin II. This effect is reverted by L-N'nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. L-arginine injection (100 ng) into the preoptic area inhibits water intake induced by water deprivation. These data show that brain NO may be an important mediator involved in drinking behaviour in the rat.
STIMULATION OF NITRIC OXIDE-DEPENDENT NEURONS AND ASTROCYTES IN CULTURE
CYCLIC GMP FORMATION IN
Agustina Garcia & Luis Agull lnstituto Biologfa Fundamental & Departamento de Bioquimica y Biologfa Molecular, Universidad Autonoma de Barcelona, Spain. We have examined the ability of several neuromodulators to stimulate nitric oxidedependent cyclic GMP accumulation in neuronal and astrocyte-enriched cultures from rat cerebrum. Glutamate was the only agonist eliciting a response in neurons (750 f 185 %, of basal levels, n=7) whereas noradrenaline (458 f 29 %, n=20) as well as glutamate (207 + 25 %, n=8) had an effect in astrocytes. The responses to glutamate were inhibited by NG-monomethyl-L-arginine (L-NMMA) and mediated by NMDA receptors in neurons and by quisqualate AMPA-insensitive receptors in astrocytes. The noradrenaline effect in astrocytes (EC,,=1.2 f 0.3 PM, n=3) was inhibited by L-NMMA (IC,,=3.1 + 1.0 FM, n=3) and haemoglobin (l&,=24.7 f 0.7 nM, n-2) and potentiated by superoxide dismutase (>I0 lJ/f,u). This response was predominantly mediated by g-adrenoceptors and to a small extent by O-receptors; it was dependent on extracellular calcium and largely inhibited by pretreatment of the cells with pertussis toxin (300 rig/ml; 18-24 h) and phorbol 12-myristate la-acetate (0.2 FM; 15 min). When the noradrenaline effect was examined in astrocytes prepared from different brain regions the higher response was observed in cerebellum (1400%) and hippocampus (970%) and the lowest in cortex (320%). These results indicate that nitric oxide synthesis as well as cyclic GMP formation can operate both in neurons and in astrocytes and that different receptors are involved.
Pharmacological Research, Vol. 26, Supplement I, 1992 BRAIN NITRIC
OXIDE AND INGESTIVE BEHAVIOUR
F. Syuadrito. Institute of Pharmacology, ITALY.
School
of Medicine,
University
of Messina,
Nitric oxide (NO) synthase has been found in the brain. However the biological significance of NO presence in the Central Nervous System (CNS) has not been fully understood. We investigated its i volvement in drinking and feeding behaviour. Feedins behaviour: 8 an inhibitor of NO synthase, N -nitro-L-arginine (L-NO Arg), inhibited food intake in food deprived rats in a dose dependent manner. This effect was reverted by the administration of LFurthermore the administration of arginine (the NO precursor). L-NO Arg increased serotonin (5-HT) utilization in several brain .areas. In addition L-NO Arg suppressing effects on food intake were abated by a pretreatment with metergoline but not with ritanserin. Brain NO may therefore modulate 5-HT during feeding L-arginine inhibited, in a dosebehaviour. Drinkina behaviour: dependent manner,. water intake induced by water deprivation or by CNS administered angiotensin II. This effect is reverted by L-N'nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase. L-arginine injection (100 ng) into the preoptic area inhibits water intake induced by water deprivation. These data show that brain NO may be an important mediator involved in drinking behaviour in the rat.
STIMULATION OF NITRIC OXIDE-DEPENDENT NEURONS AND ASTROCYTES IN CULTURE
CYCLIC GMP FORMATION IN
Agustina Garcia & Luis Agull lnstituto Biologfa Fundamental & Departamento de Bioquimica y Biologfa Molecular, Universidad Autonoma de Barcelona, Spain. We have examined the ability of several neuromodulators to stimulate nitric oxidedependent cyclic GMP accumulation in neuronal and astrocyte-enriched cultures from rat cerebrum. Glutamate was the only agonist eliciting a response in neurons (750 f 185 %, of basal levels, n=7) whereas noradrenaline (458 f 29 %, n=20) as well as glutamate (207 + 25 %, n=8) had an effect in astrocytes. The responses to glutamate were inhibited by NG-monomethyl-L-arginine (L-NMMA) and mediated by NMDA receptors in neurons and by quisqualate AMPA-insensitive receptors in astrocytes. The noradrenaline effect in astrocytes (EC,,=1.2 f 0.3 PM, n=3) was inhibited by L-NMMA (IC,,=3.1 + 1.0 FM, n=3) and haemoglobin (l&,=24.7 f 0.7 nM, n-2) and potentiated by superoxide dismutase (>I0 lJ/f,u). This response was predominantly mediated by g-adrenoceptors and to a small extent by O-receptors; it was dependent on extracellular calcium and largely inhibited by pretreatment of the cells with pertussis toxin (300 rig/ml; 18-24 h) and phorbol 12-myristate la-acetate (0.2 FM; 15 min). When the noradrenaline effect was examined in astrocytes prepared from different brain regions the higher response was observed in cerebellum (1400%) and hippocampus (970%) and the lowest in cortex (320%). These results indicate that nitric oxide synthesis as well as cyclic GMP formation can operate both in neurons and in astrocytes and that different receptors are involved.