---
_id: '1565'
abstract:
- lang: eng
  text: Leptin is an adipokine produced by the adipose tissue regulating body weight
    through its appetite-suppressing effect. Besides being expressed in the hypothalamus
    and hippocampus, leptin receptors (ObRs) are also present in chromaffin cells
    of the adrenal medulla. In the present study, we report the effect of leptin on
    mouse chromaffin cell (MCC) functionality, focusing on cell excitability and catecholamine
    secretion. Acute application of leptin (1 nm) on spontaneously firing MCCs caused
    a slowly developing membrane hyperpolarization followed by complete blockade of
    action potential (AP) firing. This inhibitory effect at rest was abolished by
    the BK channel blocker paxilline (1 μm), suggesting the involvement of BK potassium
    channels. Single-channel recordings in 'perforated microvesicles' confirmed that
    leptin increased BK channel open probability without altering its unitary conductance.
    BK channel up-regulation was associated with the phosphoinositide 3-kinase (PI3K)
    signalling cascade because the PI3K specific inhibitor wortmannin (100 nm) fully
    prevented BK current increase. We also tested the effect of leptin on evoked AP
    firing and Ca2+-driven exocytosis. Although leptin preserves well-adapted AP trains
    of lower frequency, APs are broader and depolarization-evoked exocytosis is increased
    as a result of the larger size of the ready-releasable pool and higher frequency
    of vesicle release. The kinetics and quantal size of single secretory events remained
    unaltered. Leptin had no effect on firing and secretion in db-/db- mice lacking
    the ObR gene, confirming its specificity. In conclusion, leptin exhibits a dual
    action on MCC activity. It dampens AP firing at rest but preserves AP firing and
    increases catecholamine secretion during sustained stimulation, highlighting the
    importance of the adipo-adrenal axis in the leptin-mediated increase of sympathetic
    tone and catecholamine release.
acknowledgement: "This work was supported by the Compagnia di San Paolo Foundation
  ‘Neuroscience Program’ to VC and ‘Progetto di Ateneo 2011-13’ to EC.\r\nWe thank
  Dr Claudio Franchino for cell preparation and for providing excellent technical
  support."
article_processing_charge: No
author:
- first_name: Daniela
  full_name: Gavello, Daniela
  last_name: Gavello
- first_name: David H
  full_name: Vandael, David H
  id: 3AE48E0A-F248-11E8-B48F-1D18A9856A87
  last_name: Vandael
  orcid: 0000-0001-7577-1676
- first_name: Sara
  full_name: Gosso, Sara
  last_name: Gosso
- first_name: Emilio
  full_name: Carbone, Emilio
  last_name: Carbone
- first_name: Valentina
  full_name: Carabelli, Valentina
  last_name: Carabelli
citation:
  ama: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. Dual action of leptin
    on rest-firing and stimulated catecholamine release via phosphoinositide 3-kinase-riven
    BK channel up-regulation in mouse chromaffin cells. <i>Journal of Physiology</i>.
    2015;593(22):4835-4853. doi:<a href="https://doi.org/10.1113/JP271078">10.1113/JP271078</a>
  apa: Gavello, D., Vandael, D. H., Gosso, S., Carbone, E., &#38; Carabelli, V. (2015).
    Dual action of leptin on rest-firing and stimulated catecholamine release via
    phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells.
    <i>Journal of Physiology</i>. Wiley-Blackwell. <a href="https://doi.org/10.1113/JP271078">https://doi.org/10.1113/JP271078</a>
  chicago: Gavello, Daniela, David H Vandael, Sara Gosso, Emilio Carbone, and Valentina
    Carabelli. “Dual Action of Leptin on Rest-Firing and Stimulated Catecholamine
    Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation in Mouse
    Chromaffin Cells.” <i>Journal of Physiology</i>. Wiley-Blackwell, 2015. <a href="https://doi.org/10.1113/JP271078">https://doi.org/10.1113/JP271078</a>.
  ieee: D. Gavello, D. H. Vandael, S. Gosso, E. Carbone, and V. Carabelli, “Dual action
    of leptin on rest-firing and stimulated catecholamine release via phosphoinositide
    3-kinase-riven BK channel up-regulation in mouse chromaffin cells,” <i>Journal
    of Physiology</i>, vol. 593, no. 22. Wiley-Blackwell, pp. 4835–4853, 2015.
  ista: Gavello D, Vandael DH, Gosso S, Carbone E, Carabelli V. 2015. Dual action
    of leptin on rest-firing and stimulated catecholamine release via phosphoinositide
    3-kinase-riven BK channel up-regulation in mouse chromaffin cells. Journal of
    Physiology. 593(22), 4835–4853.
  mla: Gavello, Daniela, et al. “Dual Action of Leptin on Rest-Firing and Stimulated
    Catecholamine Release via Phosphoinositide 3-Kinase-Riven BK Channel up-Regulation
    in Mouse Chromaffin Cells.” <i>Journal of Physiology</i>, vol. 593, no. 22, Wiley-Blackwell,
    2015, pp. 4835–53, doi:<a href="https://doi.org/10.1113/JP271078">10.1113/JP271078</a>.
  short: D. Gavello, D.H. Vandael, S. Gosso, E. Carbone, V. Carabelli, Journal of
    Physiology 593 (2015) 4835–4853.
date_created: 2018-12-11T11:52:45Z
date_published: 2015-11-15T00:00:00Z
date_updated: 2025-09-23T08:30:00Z
day: '15'
department:
- _id: PeJo
doi: 10.1113/JP271078
external_id:
  isi:
  - '000365267700003'
  pmid:
  - '26282459'
intvolume: '       593'
isi: 1
issue: '22'
language:
- iso: eng
main_file_link:
- open_access: '1'
  url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4650409/
month: '11'
oa: 1
oa_version: Submitted Version
page: 4835 - 4853
pmid: 1
publication: Journal of Physiology
publication_status: published
publisher: Wiley-Blackwell
publist_id: '5606'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Dual action of leptin on rest-firing and stimulated catecholamine release via
  phosphoinositide 3-kinase-riven BK channel up-regulation in mouse chromaffin cells
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 593
year: '2015'
...