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(αo) -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 α-helix that resembles the intracellular loops of G protein-coupled adrenergic receptors. Consequently, the presence of adrenoceptors and the presence of an endogenous β-adrenergic agonist at the SV membrane is suggested. Immunoblot analysis of SV using β-adrenergic receptor antibody, and vesicle swelling experiments using β-adrenergic agonists and antagonists, demonstrate the presence of functional β-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(αo) -mediated swelling of SV, participation of an endogenous β-adrenergic agonist, in the binding and stimulation of its receptor to initiate the swelling cascade is demonstrated.
Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Zhi Hui
ZH
Chen
Jin-Sook
JS
Lee
Leah
L
Shin
Won Jin
WJ
Cho
Bhanu P
BP
Jena
D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000526:Alprenolol / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D051403:Aquaporin 6 / Q000378:metabolism; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D015151:Immunoblotting; D047468:Immunoprecipitation; D007545:Isoproterenol / Q000378:metabolism / Q000494:pharmacology; D018625:Microscopy, Atomic Force; D046529:Microscopy, Electron, Transmission; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism* / Q000648:ultrastructure; D014862:Wasp Venoms / Q000378:metabolism / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D051403:Aquaporin 6; D018377:Neurotransmitter Agents; D010455:Peptides; D018343:Receptors, Adrenergic, beta-2; D014862:Wasp Venoms; D006160:Guanosine Triphosphate; D000526:Alprenolol; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D007545:Isoproterenol