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Possible Role of 5'-Adenosine Triphosphate in Synchronization of Ca²⁺ Oscillations in Primate Luteinizing Hormone-Releasing Hormone Neurons

Wisconsin National Primate Research Center (E.T., K.L.K., R.L.G., T.G.G.), and Departments of Pediatrics (E.T.) and Obstetrics and Gynecology (T.G.G.), University of Wisconsin, Madison, Wisconsin 53715-1299

Address all correspondence and requests for reprints to: Ei Terasawa, Wisconsin Regional Primate Research Center, University of Wisconsin, 1223 Capitol Court, Madison, Wisconsin 53715-1299. E-mail: terasawa{at}primate.wisc.edu.

LHRH neurons derived from the olfactory placode region of monkey embryos exhibit spontaneous intracellular Ca²⁺ ([Ca²⁺]_i) oscillations that synchronize among LHRH neurons and nonneuronal cells at a frequency similar to pulsatile LHRH release. To understand the mechanism of intercellular communication between LHRH neurons and nonneuronal cells, which leads to synchronization, we examined the possible role of ATP. 1) ATP, not ADP or AMP, stimulated both LHRH release and [Ca²⁺]_i concentration, whereas the ATP-induced [Ca²⁺]_i response was abolished by infusion of apyrase, which hydrolyzes ATP; 2) the ATP-induced [Ca²⁺]_i response occurred in normal (but not low) extracellular Ca²⁺ and was blocked by the voltage-dependent L-type Ca²⁺ channel blocker, nifedipine; 3) pharmacological experiments with purinergic receptor agonists and antagonists indicated that the ATP-induced [Ca²⁺]_i response in LHRH neurons was mediated through P2X, but not P2Y, receptors; 4) cloning and sequencing studies suggested that P2X₂ and P2X₄ transcripts were present in olfactory placode cultures; and 5) P2X₂ receptors and P2X₄ were expressed in LHRH neurons. The results suggest that ATP may play a role in intercellular communication when LHRH neurons synchronize, and raise the possibility that nonneuronal cells, such as glia, may be a crucial component of the in vivo LHRH neurosecretory system.

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