GABA in the Endocrine Pancreas : Its Putative Role as an Islet Cell Paracrine-signalling Molecule

γ-Aminobutyric acid (GABA) is a principal nonpeptidal neurotransmitter with a well-characterized role as an inhibitor of neuronal firing in the CNS (Cherubini et al., 1991; Thomas-Reetz and De Camilli, 1994). GABA is also found in other tissues, such as the endocrine pancreas (Thomas-Reetz and De Camilli, 1994). In the neuron, GABA is synthesized in close proximity to synaptic vesicles, it is produced from glutamate by the enzyme glutamate decarboxylase (GAD) and then transported into the synaptic vesicles against a proton electrochemical gradient (Thomas-Reetz and De Camilli, 1994). Exocytosis of neuronal synaptic vesicles is triggered when voltage-sensitive calcium channels open, causing a transient increase in cytosolic calcium. GABA is consequently released into the synaptic space, where it interacts with ionotropic receptors on the postsynaptic membrane, increasing their chloride conductance and thereby inducing membrane hyperpolarization and inhibition of exocytosis (...