Substance P and somatostatin inhibit calcium channels in rat sympathetic neurons via different G protein pathways.
We studied inhibition of N-type Ca2+ channels in rat superior cervical ganglion neurons by substance P (SP) and somatostatin-14 (Som). In whole-cell clamp, 70 of 82 acutely dissociated neurons showed inhibition (mean 37%) by 500 nM SP, and 54 of 61 showed inhibition by 240 nM Som (mean 57%). Pertussis toxin (PTX) blocked Som but not SP inhibition; intracellular dialysis with 2 mM GDP-beta-S attenuated inhibition with either peptide. Inhibition was voltage dependent with Som but not with SP. Neurokinin A (1 microM) or B was without effect, implicating NK1 tachykinin receptors. In cell-attached patches with bath-applied drugs, to test for a diffusible messenger, inhibition by SP or Som was only 8%. Thus, SP signaling is voltage independent and PTX insensitive; Som inhibition is voltage dependent and PTX sensitive; and both are membrane delimited.
Shapiro
M S
MS
Department of Physiology and Biophysics, University of Washington, Seattle 98195.
Hille
B
B
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D003956:Dialysis; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000166:cytology*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D037342:Pertussis Toxin; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology; D013004:Somatostatin / Q000494:pharmacology*; D013373:Substance P / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D015220:Calcium Channels; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D013373:Substance P; D013004:Somatostatin; D004533:Egtazic Acid; C023427:guanosine 5'-O-(2-thiodiphosphate); D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid