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Neurohypophyseal Hormones:From Genomics and Physiology to Disease

Simultaneous exposure to ATP and phenylephrine induces a sustained elevation in the intracellular calcium concentration in supraoptic neurons

Department of Physiology and Biophysics, University of Colorado at Denver and Health Sciences Center, Aurora, Colorado

Submitted 11 October 2005 ; accepted in final form 23 January 2006

Vasopressin (VP) release from the hypothalamo-neurohypophyseal system (HNS) is stimulated by ATP activation of P_2X purinergic receptors and by activation of 1-adrenergic receptors by phenylephrine (PE). These responses are potentiated by simultaneous exposure to ATP+PE. Potentiation was blocked by depleting intracellular calcium stores with thapsigargin. To test the hypothesis that the synergistic response to ATP+PE reflects alterations in the intracellular calcium concentration ([Ca²⁺]_i), [Ca²⁺]_i was monitored in supraoptic neurons in HNS explants loaded with fura 2-AM. Both ATP and PE induced rapid, but transient, elevations in [Ca²⁺]_i. In 0.3 mM Ca²⁺, the peak response to ATP was greater than to PE but did not differ from the peak response to ATP+PE. A sustained elevation in [Ca²⁺]_i was induced by ATP+PE, that was greater than ATP or PE alone. In 2 mM Ca²⁺, the peak response to ATP+PE was significantly greater than to either ATP or PE alone, and the sustained response to ATP+PE was greater than to either agent alone. Responses were comparable in the presence of TTX. The sustained elevation in [Ca²⁺]_i was also observed when ATP+PE was removed after 1 min, but it was eliminated by either thapsigargin or removing external calcium, indicating that both calcium influx and calcium release from internal stores are required. Some cells were vasopressinergic based on a VP-induced increase in [Ca²⁺]_i. These observations support the hypothesis that simultaneous exposure to ATP+PE induces a different pattern of [Ca²⁺]_i than either agent alone that may initiate events leading to synergistic stimulation of VP release.

vasopressin; oxytocin; norepinephrine; posterior pituitary; fura-2AM

This article has been cited by other articles:

				D. A. Gomes, Z. Song, W. Stevens, and C. D. Sladek Sustained stimulation of vasopressin and oxytocin release by ATP and phenylephrine requires recruitment of desensitization-resistant P2X purinergic receptors Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2009; 297(4): R940 - R949. [Abstract] [Full Text] [PDF]

				Z. Song, D. A. Gomes, and W. Stevens Role of purinergic P2Y1 receptors in regulation of vasopressin and oxytocin secretion Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2009; 297(2): R478 - R484. [Abstract] [Full Text] [PDF]

				Z. Song, S. Vijayaraghavan, and C. D. Sladek ATP increases intracellular calcium in supraoptic neurons by activation of both P2X and P2Y purinergic receptors Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2007; 292(1): R423 - R431. [Abstract] [Full Text] [PDF]