Modulation by oxytocin of ATP-activated currents in rat dorsal root ganglion neurons.
The modulatory effect of oxytocin (OT) on ATP-activated currents (I(ATP)) was studied in freshly isolated dorsal root ganglion (DRG) neurons of rats using whole cell clamp technique. In most of the neurons examined (50/70, 71.4%) extracellular application of OT (10(-9)-10(-5) mol/L) suppressed I(ATP) while in the rest (20/70, 28.6%) no modulatory effect was observed. OT shifted the ATP concentration-response curve downwards with a decrease of 39.8+/-4.2% in the maximal current response and with no significant change of Kd value. This OT-induced inhibition of I(ATP) showed no voltage dependence, and could be blocked by [d(CH(2))(5),Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]-OVT (d(CH(2))(5)-OVT) (10(-8) mol/L), a specific OT receptor antagonist. Intracellular application of H-9 (4 x 10(-5) mol/L, an inhibitor of protein kinase A) (n=12), BAPTA (10(-2) mol/L, a chelator of calcium ions) (n=4) could reverse the inhibitory effect of extracellular OT (10(-7) mol), while inclusion of H-7 (2 x 10(-5) mol/L, a protein kinase C inhibitior) (n=8) and KN-93 (10(-5) mol/L, an inhibitor of CaMKII) (n=9) in the recording pipette did not affect this effect. The results suggested that OT inhibition on ATP-activated currents was mediated by OT receptors in the membrane of DRG neurons; and this inhibitory effect involved the transduction of intracellular cAMP-PKA and Ca(2+).
Yang
Qing
Q
Department of Physiology, Medical College of Wuhan University, Wuhan, People's Republic of China.
Wu
Zi-Zhen
ZZ
Li
Xiao
X
Li
Zhi-Wang
ZW
Wei
Jin-Bo
JB
Hu
Qi-Sheng
QS
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D010121:Oxytocin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018045:Receptors, Oxytocin / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D007473:Ion Channels; D018045:Receptors, Oxytocin; D010121:Oxytocin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases