G proteins couple alpha-adrenergic and GABAb receptors to inhibition of peptide secretion from peripheral sensory neurons.
Regulation of neuronal calcium channels by GTP-binding proteins (G proteins) is likely to be an important mechanism by which inhibitory transmitters influence excitation-secretion coupling in presynaptic nerve endings. Here, we report that in peripheral sensory neurons from embryonic chick dorsal root ganglia (DRG), the G protein-mediated inhibition of voltage-dependent calcium channels may best explain how norepinephrine (NE) and GABA inhibit the electrically evoked, calcium-dependent release of substance P (SP). As is the case for the previously reported inhibitory actions of these transmitters on DRG cell calcium channels, we demonstrate that NE and GABA inhibit peptide secretion through activation of alpha-adrenergic and GABAb receptors that are functionally coupled to pertussis toxin (PTX)-sensitive G proteins. Pretreatment of DRG cell cultures with PTX blocked the ability of NE and GABA to inhibit the release of SP, an action correlated with PTX-catalyzed ADP-ribosylation of membrane proteins with apparent molecular weight (Mr) of 40-41 kDa. Western immunoblot analysis of chick DRG cell membrane proteins using antisera directed against synthetic peptides corresponding to amino acid sequences predicted from cDNAs for PTX-sensitive G protein alpha subunits revealed a minimum of 2 Gi-like proteins (Mr 40 and 41 kDa) and a third Go-like protein (Mr 40 kD). Significantly, these findings implicate Gi- and/or Go-like GTP-binding proteins as mediators of presynaptic inhibition in peripheral sensory neurons.
Holz
G G
GG
Department of Physiology, Tufts University School of Medicine-New England Medical Center, Boston, Massachusetts 02111.
Kream
R M
RM
Spiegel
A
A
Dunlap
K
K
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D002642:Chick Embryo; D004558:Electric Stimulation; D019204:GTP-Binding Proteins / Q000276:immunology / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology; D037342:Pertussis Toxin; D011941:Receptors, Adrenergic / Q000378:metabolism; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011963:Receptors, GABA-A / Q000378:metabolism / Q000502:physiology*; D013373:Substance P / Q000037:antagonists & inhibitors / Q000378:metabolism; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D008565:Membrane Proteins; D009479:Neuropeptides; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D011963:Receptors, GABA-A; D010566:Virulence Factors, Bordetella; D000246:Adenosine Diphosphate Ribose; D013373:Substance P; D005680:gamma-Aminobutyric Acid; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009638:Norepinephrine