Roles of connexins and pannexins in (neuro)endocrine physiology.

International audienceTo ensure appropriate secretion in response to organismal demand, (neuro)endocrine tissues liberate massive quantities of hormone, which act to coordinate and synchronize biological signals in distant secretory and non-secretory cell populations. Intercellular communication plays a central role in this control. With regard to molecular identity, junctional cell-cell communication is supported by connexin (Cx)-based gap junctions. In addition, connexin hemichannels, the structural precursors of gap junctions, as well as pannexin (Panx) channels have recently emerged as possible modulators of the secretory process. This review focuses on the expression of connexins and pannexins in various (neuro)endocrine tissues, including the adrenal cortex and medulla, the anterior pituitary, the endocrine hypothalamus and the pineal, thyroid and parathyroid glands. In response to a physiological or pathological situation, junctional intercellular coupling can be acutely modulated or persistently remodelled, thus offering multiple regulatory possibilities. The functional role(s) of gap junction-mediated intercellular communication in endocrine physiology, as well as the involvement of connexin/pannexin-related hemichannels are also discussed

Cell networks in endocrine/neuroendocrine gland function

Reproduction, growth, stress, and metabolism are determined by endocrine/neuroendocrine systems that regulate circulating hormone concentrations. All these systems generate rhythms and changes in hormone pulsatility observed in a variety of pathophysiological states. Thus, the output of endocrine/neuroendocrine systems must be regulated within a narrow window of effective hormone concentrations but must also maintain a capacity for plasticity to respond to changing physiological demands. Remarkably most endocrinologists still have a "textbook" view of endocrine gland organization which has emanated from 20<sup>th</sup> century histological studies on thin 2D tissue sections. However, 21<sup>st</sup> -century technological advances, including in-depth 3D imaging of specific cell types have vastly changed our knowledge. We now know that various levels of multicellular organization can be found across different glands, that organizational motifs can vary between species and can be modified to enhance or decrease hormonal release. This article focuses on how the organization of cells regulates hormone output using three endocrine/neuroendocrine glands that present different levels of organization and complexity: the adrenal medulla, with a single neuroendocrine cell type; the anterior pituitary, with multiple intermingled cell types; and the pancreas with multiple intermingled cell types organized into distinct functional units. We give an overview of recent methodologies that allow the study of the different components within endocrine systems, particularly their temporal and spatial relationships. We believe the emerging findings about network organization, and its impact on hormone secretion, are crucial to understanding how homeostatic regulation of endocrine axes is carried out within endocrine organs themselves

G-protein-independent signaling mediated by metabotropic glutamate receptors.

Synaptically released glutamate activates ionotropic and metabotropic receptors at central synapses. Metabotropic glutamate receptors (mGluRs) are thought to modulate membrane conductances through transduction cascades involving G proteins. Here we show, in CA3 pyramidal cells from rat hippocampus, that synaptic activation of type 1 mGluRs by mossy fiber stimulation evokes an excitatory postsynaptic response independent of G-protein function, while inhibiting an afterhyperpolarization current through a G-protein-coupled mechanism. Experiments using peptide activators and specific inhibitors identified a Src-family protein tyrosine kinase as a component of the G-protein-independent transduction pathway. These results represent the first functional evidence for a dual signaling mechanism associated with a heptahelical receptor such as mGluR1, in which intracellular transduction involves activation of either G proteins or tyrosine kinases

Chemical Synthesis of Lesion-Containing Oligonucleotides for {DNA} Repair Studies

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