Extracellular cAMP inhibits P2X receptors in rat sensory neurones through G protein-mediated mechanism.
OBJECTIVE
To identify the mechanisms of P2X(3) receptor inhibition by extracellular cyclic adenosine monophosphate (cAMP) in rat dorsal root ganglion (DRG) neurones.


METHODS
Whole-cell currents were measured in cultured DRG neurones using the combination of voltage and concentration clamp.


RESULTS
We have found that extracellular cAMP inhibits P2X(3)-mediated currents in a concentration- and use-dependent manner. The P2X(3) currents, activated by ATP applied every 4 min, were inhibited by 55% in the presence of 10 microm cAMP and by 81% in the presence of 30 microm cAMP. At 8 min interval between ATP applications the same concentration of cAMP did not alter the currents. Addition of 0.5 mm of guanosine 5'-O-(2-thiodiphosphate) to intracellular solution blocked the inhibitory action of cAMP. The inhibitory effects of cAMP were not mimicked by extracellular application of 30 mum adenosine.


CONCLUSIONS
In this paper, we demonstrate, for the first time, that extracellular application of cAMP to rat sensory neurones inhibits P2X(3) receptors via a G protein-coupled mechanism in a use-dependent manner, thus indicating the neuronal expression of specific plasmalemmal cAMP receptor.
Mamenko
M V
MV
Bogomoletz Institute of Physiology, Kiev, Ukraine.
Chizhmakov
I V
IV
Volkova
T M
TM
Verkhratsky
A
A
Krishtal
O A
OA
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058477:Receptors, Purinergic P2X3; D015290:Second Messenger Systems / Q000187:drug effects*; D011984:Sensory Receptor Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
C546410:P2rx3 protein, rat; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000242:Cyclic AMP; D019204:GTP-Binding Proteins