Penicillin G Induces H+, K+-ATPase via a Nitric Oxide-Dependent Mechanism in the Rat Colonic Crypt

© Copyright by the Author(s). Published by Cell Physiol Biochem Press..

BACKGROUND/AIMS: The colonic H+, K+ ATPase (HKA2) is a heterodimeric membrane protein that exchanges luminal K+ for intracellular H+ and is involved in maintaining potassium homeostasis. Under homeostatic conditions, the colonic HKA2 remains inactive, since most of the potassium is absorbed by the small intestine. In diarrheal states, potassium is secreted and compensatory potassium absorption becomes necessary. This study proposes a novel mechanism whereby the addition of penicillin G sodium salt (penG) to colonic crypts stimulates potassium uptake in the presence of intracellular nitric oxide (NO), under sodium-free (0-Na+) conditions.

METHODS: Sprague Dawley rat colonic crypts were isolated and pHi changes were monitored through the ammonium prepulse technique. Increased proton extrusion in 0-Na+ conditions reflected heightened H+, K+ ATPase activity. Colonic crypts were exposed to penG, L-arginine (a NO precursor), and N-nitro l-arginine methyl ester (L-NAME, a NO synthase inhibitor).

RESULTS: Isolated administration of penG significantly increased H+, K+ ATPase activity from baseline, p 0.0067. Co-administration of arginine and penG in 0-Na+ conditions further upregulated H+, K+ ATPase activity, p <0.0001. Crypt perfusion with L-NAME and penG demonstrated a significant reduction in H+, K+ ATPase activity, p 0.0058.

CONCLUSION: Overall, acute exposure of colonic crypts to penG activates the H+, K+ ATPase in the presence of NO. This study provides new insights into colonic potassium homeostasis.

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:54

Enthalten in:

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology - 54(2020), 6 vom: 12. Nov., Seite 1132-1142

Sprache:

Englisch

Beteiligte Personen:

Baratta, Vanessa M [VerfasserIn]
Norz, Valentina [VerfasserIn]
Barahona, Maria J [VerfasserIn]
Gisinger, Teresa M [VerfasserIn]
Mulligan, David [VerfasserIn]
Geibel, John P [VerfasserIn]

Links:

Volltext

Themen:

(3-5) Fluid secretion; H+, K+ ATPase; Nitric oxide pathway; Penicillin G; Colon
31C4KY9ESH
94ZLA3W45F
Arginine
EC 3.6.3.10
H(+)-K(+)-Exchanging ATPase
Journal Article
NG-Nitroarginine Methyl Ester
Nitric Oxide
Penicillin G
Q42T66VG0C
V55S2QJN2X

Anmerkungen:

Date Completed 27.05.2021

Date Revised 20.09.2021

published: Print

Citation Status MEDLINE

doi:

10.33594/000000305

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM317431021