Endogenous ATP potentiates only vasopressin secretion from neurohypophysial terminals.
Exogenous ATP induces inward currents and causes the release of arginine-vasopressin (AVP) from isolated neurohypophysial terminals (NHT); both effects are inhibited by the P2X2 and P2X3 antagonists, suramin and PPADS. Here we examined the role of endogenous ATP in the neurohypophysis. Stimulation of NHT caused the release of both AVP and ATP. ATP induced a potentiation in the stimulated release of AVP, but not of oxytocin (OT), which was blocked by the presence of suramin. In loose-patch clamp recordings, from intact neurohypophyses, suramin or PPADS produces an inhibition of action potential currents in a static bath, that can be mimicked by a hyperpolarization of the resting membrane potential (RMP). Correspondingly, in a static versus perfused bath there is a depolarization of the RMP of NHT, which was reduced by either suramin or PPADS. We measured an accumulation of ATP (3.7 +/- 0.7 microM) released from NHT in a static bath. Applications of either suramin or PPADS to a static bath decreased burst-stimulated capacitance increases in NHT. Finally, only vasopressin release from electrically stimulated intact neurohypophyses was reduced in the presence of Suramin or PPADS. These data suggest that there was sufficient accumulation of ATP released from the neurohypophysis during stimulations to depolarize its nerve terminals. This would occur via the opening of P2X2 and P2X3 receptors, inducing an influx of Ca2+. The subsequent elevation in [Ca2+](i) would further increase the stimulated release of only vasopressin from NHT terminals. Such purinergic feedback mechanisms could be physiologically important at most CNS synapses.
Knott
Thomas K
TK
Department of Physiology & Program in Neuroscience, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655, USA.
Marrero
Héctor G
HG
Custer
Edward E
EE
Lemos
José R
JR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001127:Arginine Vasopressin / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D018408:Patch-Clamp Techniques; D010904:Pituitary Gland, Posterior / Q000187:drug effects / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000187:drug effects / Q000378:metabolism; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D013498:Suramin / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism*
D000970:Antineoplastic Agents; D010975:Platelet Aggregation Inhibitors; D018048:Receptors, Purinergic P2; D058476:Receptors, Purinergic P2X2; D058477:Receptors, Purinergic P2X3; D014667:Vasopressins; D001127:Arginine Vasopressin; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D010121:Oxytocin; D011732:Pyridoxal Phosphate; D013498:Suramin; D000255:Adenosine Triphosphate