Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells

Christopher M. Breen, Peter J. Mannon, Bruce A. Benjamin

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B, Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (I(sc)) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline I(sc), nor did it alter I(sc) in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (I(sc)/(Cl)) was stimulated with AVP (10 nM) added to the basolateral surface and 10 μM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of I(sc)/(Cl), with the maximal inhibitory dose (100 nM) causing 52 ± 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of I(sc)/(Cl) is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of I(sc)/(Cl) was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% ± 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of I(sc)/(Cl). We conclude that PYY acts through either G(i) or G(o) to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.

Original languageEnglish
Pages (from-to)F452-F457
JournalAmerican Journal of Physiology - Renal Physiology
Volume275
Issue number3 44-3
StatePublished - 1 Sep 1998

Fingerprint

Peptide YY
Vasopressins
Chlorides
Electrolytes
Inhibitory Concentration 50
Sodium
Kidney
Amiloride
Pertussis Toxin
Adenylyl Cyclases

Keywords

  • Adenosine 3',5'-cyclic monophosphate
  • Arginine vasopressin
  • Chloride secretion
  • Short-circuit current

Cite this

@article{04ea9fcb8bf24e8dab5be303e04601f6,
title = "Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells",
abstract = "mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B, Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (I(sc)) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline I(sc), nor did it alter I(sc) in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (I(sc)/(Cl)) was stimulated with AVP (10 nM) added to the basolateral surface and 10 μM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of I(sc)/(Cl), with the maximal inhibitory dose (100 nM) causing 52 ± 1.3{\%} inhibition (IC50 = 0.11 nM). Inhibition by PYY of I(sc)/(Cl) is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of I(sc)/(Cl) was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38{\%} ± 6{\%} inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of I(sc)/(Cl). We conclude that PYY acts through either G(i) or G(o) to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.",
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Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells. / Breen, Christopher M.; Mannon, Peter J.; Benjamin, Bruce A.

In: American Journal of Physiology - Renal Physiology, Vol. 275, No. 3 44-3, 01.09.1998, p. F452-F457.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Peptide YY inhibits vasopressin-stimulated chloride secretion in inner medullary collecting duct cells

AU - Breen, Christopher M.

AU - Mannon, Peter J.

AU - Benjamin, Bruce A.

PY - 1998/9/1

Y1 - 1998/9/1

N2 - mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B, Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (I(sc)) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline I(sc), nor did it alter I(sc) in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (I(sc)/(Cl)) was stimulated with AVP (10 nM) added to the basolateral surface and 10 μM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of I(sc)/(Cl), with the maximal inhibitory dose (100 nM) causing 52 ± 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of I(sc)/(Cl) is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of I(sc)/(Cl) was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% ± 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of I(sc)/(Cl). We conclude that PYY acts through either G(i) or G(o) to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.

AB - mIMCD-k2 cells are derived from the inner medullary collecting duct of a mouse and exhibit electrogenic sodium absorption and cAMP- and vasopressin (AVP)-stimulated electrogenic chloride secretion [N. L. Kizer, B. Lewis, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F347-F355, 1995; and N. L. Kizer, D. Vandorpe, B, Lewis, B. Bunting, J. Russell, and B. A. Stanton. Am. J. Physiol. 268 (Renal Fluid Electrolyte Physiol. 37): F854-F861, 1995]. The purpose of the present study was to determine how peptide YY (PYY) affects electrogenic Na+ and Cl- current in mIMCD-k2 cells. Short-circuit currents (I(sc)) were measured across monolayers of mIMCD-k2 cells mounted in Ussing-type chambers. PYY did not alter baseline I(sc), nor did it alter I(sc) in chloride-free conditions, indicating no effect on electrogenic sodium transport. Baseline chloride current in these cells is low; therefore, chloride short-circuit current (I(sc)/(Cl)) was stimulated with AVP (10 nM) added to the basolateral surface and 10 μM amiloride added to the apical surface. Although apical applications of PYY had no effect, basolateral application of PYY caused attenuation of I(sc)/(Cl), with the maximal inhibitory dose (100 nM) causing 52 ± 1.3% inhibition (IC50 = 0.11 nM). Inhibition by PYY of I(sc)/(Cl) is mediated through the Y2 receptor subtype, as PYY-(3-36) was the only PYY analog tested that caused inhibition and was equipotent to PYY. Inhibition by PYY of I(sc)/(Cl) was abolished following incubation with pertussis toxin. We also show that PYY inhibits AVP-stimulated cAMP accumulation, with a maximal inhibitory dose (100 nM) causing a 38% ± 6% inhibition (IC50 = 0.16 nM), comparable to inhibition by PYY of I(sc)/(Cl). We conclude that PYY acts through either G(i) or G(o) to inhibit adenylate cyclase activity, leading to a decrease in AVP-stimulated chloride current.

KW - Adenosine 3',5'-cyclic monophosphate

KW - Arginine vasopressin

KW - Chloride secretion

KW - Short-circuit current

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SP - F452-F457

JO - American Journal of Physiology - Renal Physiology

JF - American Journal of Physiology - Renal Physiology

SN - 0363-6127

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