The effect of the neuropeptide substance P on desensitization of ATP receptors of PC12 cells.
1. Patch clamp recording (whole cell configuration) was employed to investigate the modulatory action of substance P on inward currents elicited by adenosine 5'-triphosphate (ATP, focally applied via a pressure pipette) from phaechromocytoma (PC12) cells usually held at -70 mV. 2. Bath-applied substance P (0.2-20 microM) had no effect on baseline membrane current but reversibly reduced ATP peak currents in a concentration-dependent fashion. The depressant effect was not associated with a change in the ATP current reversal potential. 3. Equiamplitude peak responses induced by 50 microM or 5 mM ATP were differentially affected by substance P which preferentially reduced currents evoked by 5 mM ATP. In the presence of substance P a conditioning pulse of ATP evoked a stronger depression to subsequent test pulses of the same agonist. 4. Combined patch clamping and confocal laser imaging of intracellular Ca2+ ([Ca2+]i) of single PC12 cells showed that substance P (applied by a pressure pipette) per se had no effect on [Ca2+]i or current baseline, although it reduced the inward current and associated [Ca2+]i rise elicited by ATP. 5. These results are interpreted as due to facilitation by substance P of desensitization of ATP-gated P2x2 receptors of PC12 cells. It is proposed that the novel modulation by this peptide of ATP responses may serve as a model for further studies aimed at elucidating the action of substance P on purinergic neurotransmission.
Khiroug
L
L
Biophysics Sector, International School for Advanced Studies (SISSA), Trieste, Italy.
Giniatullin
R
R
Talantova
M
M
Nistri
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016716:PC12 Cells; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000187:drug effects* / Q000502:physiology; D058476:Receptors, Purinergic P2X2; D013373:Substance P / Q000494:pharmacology*
D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D013373:Substance P; D000255:Adenosine Triphosphate