ABSTRACT
The aim of the present study was to give a better characterization of GABA receptors that modulate aminergic release. GABA or muscimol (15 microM) increased basal noradrenaline (3H-NA) release but reduced the following K+-evoked 3H-NA release in the synaptosomes from rat cerebellar cortex. Bicuculline and picrotoxin counteracted these two effects. The same GABA modulation resulted to operate also on dopaminergic and serotoninergic neuron terminals. The increased basal noradrenaline release resulted to be both calcium and chloride dependent and associated with an increased entry of 45Ca++ into the synaptosomes. We therefore advance the hypothesis of an involvement of a Cl-/Ca++ synporter system coupled to the receptor. Baclofen also reduced the K+-evoked 3H-NA release, but did not increase basal 3H-NA release; moreover, the interaction of baclofen G with GABA-B receptors resulted to be associated with the inhibition of 45Ca++ entry into synaptosomes. GABA-B receptors resulted to be present also on serotoninergic but not on dopaminergic neuron terminals. The GABA-C receptor agonist cis-4-aminocrotonic acid (CACA) did not influence either basal or K+-evoked 3H-NA release. These results point to a new type of GABA functional role through a different A-family receptor subtype, coupled with calcium influx in aminergic neuron terminals, modulating aminergic release.
Subject(s)
Calcium/pharmacokinetics , Cerebellar Cortex/metabolism , Chlorides/pharmacokinetics , Norepinephrine/metabolism , Presynaptic Terminals/metabolism , Receptors, GABA-A/metabolism , Animals , Basal Metabolism , Biogenic Amines/metabolism , Biological Transport/drug effects , Biological Transport/physiology , Cerebellar Cortex/drug effects , Cerebellar Cortex/ultrastructure , Male , Potassium/pharmacology , Presynaptic Terminals/drug effects , Rats , Rats, Wistar , Receptors, GABA-A/drug effects , Stimulation, Chemical , gamma-Aminobutyric Acid/pharmacologyABSTRACT
Our aim has been to investigate the ability of the rat brain to retain its level of neurotransmitter release over life. We have investigated the neurotransmitter release from the rat brain synaptosomes prelabeled with 3H-DA, 3H-NA, or 3H-5HT, and perfused with Krebs-Ringer medium alone (basal release) or containing a high K+, calcium ionophore, tyramine or amphetamine (evoked release). Brain areas have been dissected of animals 45 days and 4, 6, and 11 months old. The results have shown a gradual reduction of the 3H-NA release evoked by a high K+ from 45 days to 6 months, which is stabilized until 11 months of age. The reduction rate has been relatively different from the brain areas investigated (36% for the frontal cortex and 26% for the hippocampus and cerebellar cortex). A similar reduction has been seen with 3H-5HT released from synaptosomes of the frontal cortex, hippocampus, and striatum. Surprisingly, the 3H-DA release that was evoked by high K+ was greater in rats 11 months old than in younger rats; this effect has been seen in synaptosomes from the caudate and the frontal cortex. The calcium ionophore A23187 has shown a releasing picture similar to a high K+. When we analyzed a nonexocitotic, but probably carrier mediated, release (evoked by tyramine or amphetamine), there was reduced release of all of the above neurotransmitters from 45 days to 11 months of age. We presume that there have been adaptive changes in neurotransmitter evoked release due to changes in Ca++ utilization, as inferred from the results from calcium ionophore experiments and carrier performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Subject(s)
Aging/metabolism , Biogenic Monoamines/metabolism , Brain Chemistry/physiology , Dopamine/metabolism , Amphetamine/pharmacology , Animals , Calcimycin/pharmacology , Caudate Nucleus/drug effects , Caudate Nucleus/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/metabolism , Male , Nerve Endings/metabolism , Neurotransmitter Agents/metabolism , Norepinephrine/metabolism , Potassium/pharmacology , Rats , Rats, Wistar , Serotonin/metabolism , Synaptosomes/drug effects , Synaptosomes/metabolism , Tyramine/pharmacologyABSTRACT
Involvement of 5HT2 receptors in human platelet aggregation was assessed by studying the effect of ADP, epinephrine and thrombin on 3H-5HT release from platelets. The release experiments were made with a perfusion method to preserve any compound, released or formed by platelet, from interacting with platelet itself. In these conditions, aggregation does not occur, as confirmed by Scanning Electron Microscopy. These release experiments showed that the platelet activation by such agents is coupled with 5-HT release. The aggregation experiments, made on different aliquots of the same platelet-rich plasma (PRP), showed that the released 5-HT, interacting with its own receptors on platelet activated surface, determines aggregation. In fact, although it is known that 5-HT added to PRP was only able to induce a moderate platelet aggregation, the 5-HT2 antagonist ketanserin counteracted the aggregation induced by ADP, epinephrine and thrombin. These results suggest that a 5HT2 antagonist could be therapeutically important in those pathological states in which serotonin, released by activated platelets, may increase aggregation.
