Noradrenaline inhibition of Ca<sup>2+</sup> channels and secretion in single patch‐clamped insulinoma cells

Sher, Emanuele; Codignola, Agnese; Rogers, Marc; Richmond, Janet E.

doi:10.1016/0014-5793(96)00380-8

Cited by 8 publications

(4 citation statements)

References 34 publications

(58 reference statements)

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“…Thus, the expected maximal increase in C m due to fusion of the entire pool of insulin containing granules of RINm5F cells will most likely not exceed 100 fF. Although qualitatively similar results to those reported here have been shown in a study using RINm5F cells, the C m changes in RINm5F cells exceeded 1 pF and can, thus, probably not account for exocytosis of insulin granules [17]. This makes the INS‐1 cells more suitable for such studies.…”

Section: Discussionsupporting

confidence: 82%

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells

et al. 1997

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Section: Discussionsupporting

confidence: 82%

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells

et al. 1997

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“…Pancreatic β cells express a wide variety of heterotrimeric G‐proteins [198] and the role of the plasma membrane receptor activated heterotrimeric GTPases in the general regulation of insulin secretion has been fairly well investigated [9–13]. However, regulation of levels of second messengers such as Ca 2+ or cAMP cannot solely explain the observed effect of GPCR activation on secretion (for example see [199–203]). A direct control of secretion at the level of exocytosis by plasma membrane activated G‐proteins would offer several advantages to the cell.…”

Section: Heterotrimeric G‐proteins As  Regulators Of Exocytosismentioning

confidence: 99%

“…Controlled permeabilization of the cellular plasma membrane to gain access to the cytosol permits to maintain the concentrations of intracellular second messengers such as Ca 2+ or cAMP at constant levels [64]. The persistence of GPCR‐mediated inhibition of exocytosis under these circumstances indicates a general role for heterotrimeric GTPases in the direct control of secretion at a late step of exocytosis in pancreatic β cells and in the neuroendocrine clonal cell lines AtT‐20 and PC12 [199–206]. The refined analysis of the inhibitory effect in streptolysin‐O permeabilized clonal and primary β cells ruled out any participation of diffusible molecules including large cytosolic proteins and revealed that all α i isoforms and α o 2, but not α o 1, are efficient mediators of the inhibitory G i /G o effect [207].…”

Section: Heterotrimeric G‐proteins As  Regulators Of Exocytosismentioning

confidence: 99%

Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion

Lang¹

1999

European Journal of Biochemistry

320

250

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Secretion of the peptide hormone insulin from pancreatic b cells constitutes an important step in the regulation of body homeostasis. Insulin is stored in large dense core vesicles and released by exocytosis, a multistage process involving transport of vesicles to the plasma membrane, their docking, priming and finally their fusion with the plasma membrane. Some of the protein components necessary for this process have been identified in b cells. The export of potent and potentially harmful substances has to be tightly controlled. The secretory response in pancreatic b cells requires the concerted action of nutrients together with enteric hormones and neurotransmitters acting on G-protein coupled receptors. It is well established that glucose and other metabolizable nutrients depolarize the b-cell membrane and the ensuing Ca 2+ influx through voltage-dependent channels constitutes a main stimulus for insulin exocytosis. Theoretical considerations and recent observations suggest in addition an organizing role for the Ca 2+ channel similar to neurotransmission. A second regulatory control on exocytosis is exerted by monomeric and heterotrimeric G-proteins. The monomeric GTPase Rab3A controls insulin secretion through cycling between a guanosine triphosphate liganded vesicle-bound form and a guanosine diphosphate liganded, cytosolic form. The effect of neurohormones is transduced by the heterotrimeric GTPases. Whereas pertussis-toxin sensitive a-subunits exert direct inhibition at the level of exocytosis, the Gbg-subunits are required for stimulation. It is possible that these GTPases exert immediate regulation, while protein kinases and phosphatases may modulate long-term adaptation at the exocytotic machinery itself. The molecular nature of their activators and effectors still await identification. Insights into the progression of the exocytotic vesicle from docking to fusion and how these processes are precisely regulated by proteins and second messengers may provide the basis for new therapeutic principles.Keywords: calcium; exocytosis; G-proteins; hormones; insulin; membrane fusion; neurotransmission; SNARE proteins; vesicle trafficking; b cells.The process of regulated secretion forms the basis for a broad variety of physiological processes such as intracellular communication in the nervous system, acute defence against bacterial invasion and the regulation of body homeostasis by hormones. Consequently, secretory systems can be classified as myeloid, neuronal, neuroendocrine and endocrine. The best characterized endocrine system is represented by the pancreatic b cell in which the molecular basis of insulin release and its regulation has been extensively studied. The control of insulin secretion from the pancreatic b cells and the biological actions of this peptide hormone on its target tissues ensure the vital function of glucose homeostasis [1]. Insulin secretion is inadequate in various forms of diabetes, in particular in pre-type I (insulindependent diabetes mellitus) and in many forms of the more common ...

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“…Using this method, it has been shown that tolbutamide increases C m without changing the Ca 2+ -influx in mouse β cells suggesting a direct effect on exocytosis [5]. When inhibitors were applied to cells under voltage clamp and exocytosis stimulated by depolarising voltage pulses, the increase in C m was inhibited by galanin, somatostatin and α 2 -adrenoceptor activation [4,21,22]. …”

Section: Introductionmentioning

confidence: 99%

Effects of Adrenaline and Tolbutamide on Insulin Secretion in INS-1 Cells Under Voltage Control

Kampermann

Herbst²,

Ullrich³

2000

Cell Physiol Biochem

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The aim of the present study was to investigate whether mechanisms distal to the regulation of Ca²⁺-influx are involved in tolbutamide-induced stimulation and adrenaline- and somatostatin -induced inhibition of insulin secretion in INS-1 cells. Using the patch clamp method, the membrane voltage was either kept constant at –70 mV, or Ca²⁺-influx was activated by short depolarising pulses to 0 mV. These pulses induced an increase in cellular capacitance (C_m) caused by fusion of secretory granules with the plasma membrane. Tolbutamide did not alter, neither C_m under voltage clamp at –70 mV nor increases of C_m due to voltage pulses. The inhibitors of secretion, adrenaline and somatostatin, counteracted the augmentation of [Ca²⁺]_i which was induced by glucose, tolbutamide and forskolin. In the voltage clamp mode, however, where no changes of [Ca²⁺]_i were observed, adrenaline but not somatostatin inhibited the increase of C_m caused by depolarizing voltage pulses. The adrenaline effect on C_m was dependent on the addition of GTP to the pipette solution. When GTP was replaced by GDPβS or GTPγS, the effect of adrenaline on C_m was abolished. The blockade of calcineurin, by the addition of calcineurin inhibitory peptide (CIP) to the pipette solution, did not affect the adrenaline-induced inhibition of C_m. Moreover, after incubation of the cells with deltamethrin, a calcineurin inhibitor, the stimulation of secretion was attenuated, but the adrenaline-induced inhibition was not affected. Our results suggest that adrenaline-induced inhibition of insulin secretion involves a site of action directly related to the exocytotic membrane fusion. In contrast, the stimulator tolbutamide and the inhibitor somatostatin had no direct effect on exocytosis in INS-1 cells.

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Noradrenaline inhibition of Ca²⁺ channels and secretion in single patch‐clamped insulinoma cells

Cited by 8 publications

References 34 publications

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells

Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion

Effects of Adrenaline and Tolbutamide on Insulin Secretion in INS-1 Cells Under Voltage Control

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Noradrenaline inhibition of Ca2+ channels and secretion in single patch‐clamped insulinoma cells

Cited by 8 publications

References 34 publications

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca2+]i in insulin secreting cells

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca2+]i in insulin secreting cells

Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretion

Effects of Adrenaline and Tolbutamide on Insulin Secretion in INS-1 Cells Under Voltage Control

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Noradrenaline inhibition of Ca²⁺ channels and secretion in single patch‐clamped insulinoma cells

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells

Adrenaline inhibits depolarization‐induced increases in capacitance in the presence of elevated [Ca²⁺]_i in insulin secreting cells