Inhibitory Effect of Somatostatin-14 on L-Type Voltage-Gated Calcium Channels in Cultured Cone Photoreceptors Requires Intracellular Calcium
ABSTRACT The inhibitory effects of somatostatin have been well documented for many physiological processes. The action of somatostatin is through G-protein-coupled receptor-mediated second-messenger signaling, which in turn affects other downstream targets including ion channels. In the retina, somatostatin is released from a specific class of amacrine cells. Here we report that there was a circadian phase-dependent effect of somatostatin-14 (SS14) on the L-type voltage-gated calcium channels (L-VGCCs) in cultured chicken cone photoreceptors, and our study reveals that this process is dependent on intracellular calcium stores. Application of 500 nM SS14 for 2 h caused a decrease in L-VGCC currents only during the subjective night but not the subjective day. We then explored the cellular mechanisms underlying the circadian phase-dependent effect of SS14. The inhibitory effect of SS14 on L-VGCCs was mediated through the pertussis-toxin-sensitive G-protein-dependent somatostatin receptor 2 (sst2). Activation of sst2 by SS14 further activated downstream signaling involving phospholipase C and intracellular calcium stores. Mobilization of intracellular Ca2+ was required for somatostatin induced inhibition of photoreceptor L-VGCCs, suggesting that somatostatin plays an important role in the modulation of photoreceptor physiology.
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ABSTRACT: The peptide hormone somatostatin controlling functions of CNS and peripheral organs and tissues realizes its regulatory effects via five types of somatostatin receptors (SomR) coupled to heterotrimeric G-proteins. Targets of the hormone action are the enzymes generating second messengers (adenylyl cyclase, phospholipase C, phosphatidylinositol-3-kinase), phosphotyrosine phosphatases, ion channels. The review summarizes and analyzes literature data and results of our studies on molecular mechanisms of transduction of the somatostatin signal into the cell, selectivity of interaction of SomR with heterotrimeric G-proteins and intracellular effectors as well as on effect of SomR oligomerization on their functional activity.Journal of Evolutionary Biochemistry and Physiology 07/2012; 48(4). DOI:10.1134/S0022093012040020 · 0.24 Impact Factor
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ABSTRACT: Message encoding for three isoforms of somatostatin (SS) peptides, SS-14, goldfish brain (gb)SS-28 and [Pro²]SS-14, are expressed in goldfish hypothalamus and pituitary tissues. All three native goldfish SSs are active in reducing basal and stimulated growth hormone (GH) responses in cultured goldfish pituitary cells, although with different potencies and efficacies. In the present study, we examined the effects of these three endogenous SSs on electrophysiological properties of goldfish somatotrophs and their physiological relevance. Voltage-sensitive K+ , Ca²+ and Na+ channels in identified goldfish somatotrophs in primary culture were isolated using whole-cell, amphotericin B-perforated patch-clamp techniques. None of the three SSs affected Na+ currents but all three SSs increased maximal K+ current magnitude, with SS-14 being the most effective. [Pro²]SS14 did not affect Ba²+ currents through voltage-sensitive Ca²+ channels but SS14 decreased the magnitude of early and late Ba²+ currents, whereas gbSS-28 reduced that of the late Ba²+ current. Under current-clamp conditions, SS14 and gbSS28 attenuated evoked action potential magnitudes by 34% and 18%, respectively, although [Pro²]SS14 had no effects. However, all three SSs decreased basal intracellular Ca²+ levels ([Ca²+ ](i)) and suppressed basal GH release. These data suggest that, although the ability of SS-14 and gbSS-28 to decrease basal [Ca²+](i) and GH release can be explained, at least in part, by their attenuating effects on cell excitability and current flow through voltage-sensitive Ca²+ channels, [Pro²]SS14-induced reduction in GH responses and [Ca²+](i) cannot be explained by changes in Ca²+ channel properties.Journal of Neuroendocrinology 01/2011; 23(1):82-93. DOI:10.1111/j.1365-2826.2010.02073.x · 3.51 Impact Factor
- Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, 04/2011, Degree: Doctor of Philosophy, Supervisor: Dr. Wallace B. Thoreson