P2X receptor channels in endocrine glands

Abstract

The endocrine system is the system of ductless glands and single cells that synthetize hormones and release them directly into the bloodstream. Regulation of endocrine system is very complex and ATP and its degradable products ADP and adenosine contribute to its regulation acting as extracellular messengers for purinergic receptors. These include P2X receptors, a family of ligand-gated ion channels which expression and roles in endocrine tissues are reviewed here. There are seven mammalian purinergic receptor subunits, denoted P2X1 through P2X7, and the majority of these subunits are also expressed in secretory and non-secretory cells of endocrine system. Functional channels have been identified in the neuroendocrine hypothalamus, the posterior and anterior pituitary, the thyroid gland, the adrenals, the endocrine pancreas, the gonads and the placenta. Native channels are capable of promoting calcium influx through its pore in both excitable and non-excitable cells, as well as of increasing electrical activity in excitable cells by membrane depolarization. This leads to generation of calcium transients and stimulation of hormone release. The pattern of expression and action of P2XRs in endocrine system suggests that locally produced ATP amplifies and synchronizes the secretory responses of individual cells.

P2X4 Receptor Function in the Nervous System and Current Breakthroughs in Pharmacology

“…Paraventricular neurons, arcuate nucleus GnRH neurons and secretory cells of the anterior pituitary all express P2X4 as illustrated through molecular biology techniques in combination with electrophysiology ( Zemkova et al, 2010 ). Functional P2X4 receptors have also been identified in lactotrophs ( He et al, 2003 ), and in the posterior pituitary system functional P2X4 responses have been recorded from supraoptic neurons ( Vavra et al, 2011 ; Stojilkovic and Zemkova, 2013 ). P2X4 has also been demonstrated to be expressed in somatosensory cortical neurons ( Lalo et al, 2007 ), nodose ganglion neurons ( Tan et al, 2009 ), trigeminal neurons ( Luo et al, 2006 ), vestibular ganglion neurons ( Ito et al, 2010 ), retinal ganglion and bipolar cells ( Wheeler-Schilling et al, 2001 ) and in spinal cord neurons ( Bardoni et al, 1997 ; Kobayashi et al, 2005 ).…”

Roles of connexins and pannexins in (neuro)endocrine physiology

“…Moreover, full-length Panx1 as well as its truncated splice variants Panx1c and Panx1d physically associate with P 2 X 2 , P 2 X 3 , P 2 X 4 and P 2 X 7 ATP-gated purinergic channel subtypes [92]. While the roles of pannexins in pituitary cell function are not well defined, they may modulate gonadotropin, GH and PRL release, given that activation of P 2 X receptors in gonadotrophs, somatotrophs and lactotrophs induces depolarization and calcium fluxes [93][94][95][96] (Fig. 2).…”

Synthetic testosterone derivatives modulate rat P2X2 and P2X4 receptor channel gating

“…8). Thus potentiation of P2XRs that are widely expressed in neurons of many areas of the brain (Khakh and North, 2012) and neuroendocrine cells (Stojilkovic and Zemkova, 2013) might be involved in the adverse neuropsychiatric effects of anabolic steroids.…”