Involvement of β-adrenergic receptor in synaptic vesicle swelling and implication in neurotransmitter release

Secretory vesicle swelling is required for vesicular discharge during cell secretion. The G(alpha o)-mediated water channel aquaporin-6 (AQP-6) involvement in synaptic vesicle (SV) swelling in neurons has previously been reported. Studies demonstrate that in the presence of guanosine triphosphate (GTP), mastoparan, an amphiphilic tetradecapeptide from wasp venom, activates G(o) protein GTPase, and stimulates SV swelling. Stimulation of G proteins is believed to occur via insertion of mastoparan into the phospholipid membrane to form a highly structured alpha-helix that resembles the intracellular loops of G protein-coupled adrenergic receptors. Consequently, the presence of adrenoceptors and the presence of an endogenous beta-adrenergic agonist at the SV membrane is suggested. Immunoblot analysis of SV using beta-adrenergic receptor antibody, and vesicle swelling experiments using beta-adrenergic agonists and antagonists, demonstrate the presence of functional beta-adrenergic receptors at the SV membrane. Since a recent study shows vH+-ATPase to be upstream of AQP-6 in the pathway leading from G(alpha o)-mediated swelling of SV, participation of an endogenous beta-adrenergic agonist, in the binding and stimulation of its receptor to initiate the swelling cascade is demonstrated.