Neuropeptide Y stimulates renal prostaglandin synthesis in the isolated rat kidney

Contribution of Ca++ and calmodulin

M. M.M. El-Din, Kafait Malik

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Abstract

We have investigated the effects of neuropeptide Y (NPY) on vascular tone and renal output of prostaglandins (PGs) and the mechanism underlying these actions by examining the effects of Ca++ depletion, Ca++ channel blockers and calmodulin inhibitors in the isolated Tyrode's perfused rat kidney. Administration of NPY (0.23-2.3 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF(1α), the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (60 μM) or nifedipine (1.4 μM), to the perfusion fluid abolished the effects of NPY to promote renal vasoconstriction and PG synthesis. Infusion of calmodulin inhibitors, trifluoperazine (2 μM), W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] (20 μM) or calmidazolium (0.2 μM), attenuated the renal vasoconstriction and the increase in PG output produced by NPY (0.7 nmol). In kidneys perfused with normal Tyrode's solution, infusion of NPY, in a concentration (1.7 x 10-8M) that produced only a small transient increase in renal vascular tone and failed to alter the renal output of PGs, enhanced the rise in PGE2 and 6-keto-PGF(1α) elicited by norepinephrine (0.25 nmol) but not by arginine vasopressin (0.004 nmol) or angiotensin II (0.09 nmol). The renal vasoconstriction elicited by norepinephrine and arginine vasopressin as well as by angiotensin II was enhanced by NPY. In kidneys perfused with Ca++-depleted Tyrode's solution norepinephrine-induced rise in perfusion pressure was abolished whereas PG output was reduced by 25 to 30% and it was not altered by the infusion of NPY (1.7 x 10-8 M). These data suggest that NPY in large doses produces renal vasoconstriction and PG synthesis directly by a mechanism that depends primarily on extracellular Ca++ and calmodulin. However, small concentrations of NPY that are devoid of their direct effect on renal vascular tone and PG synthesis potentiates norepinephrine-induced component of PG synthesis that is dependent upon extracellular Ca++.

Original languageEnglish (US)
Pages (from-to)479-484
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume246
Issue number2
StatePublished - Jan 1 1988

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Neuropeptide Y
Calmodulin
Prostaglandins
Kidney
Vasoconstriction
Norepinephrine
Blood Vessels
Arginine Vasopressin
Prostaglandins F
Dinoprostone
Angiotensin II
calmidazolium
Perfusion
Trifluoperazine
Diltiazem
Sulfonamides
Epoprostenol
Nifedipine
Hydrolysis

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

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title = "Neuropeptide Y stimulates renal prostaglandin synthesis in the isolated rat kidney: Contribution of Ca++ and calmodulin",
abstract = "We have investigated the effects of neuropeptide Y (NPY) on vascular tone and renal output of prostaglandins (PGs) and the mechanism underlying these actions by examining the effects of Ca++ depletion, Ca++ channel blockers and calmodulin inhibitors in the isolated Tyrode's perfused rat kidney. Administration of NPY (0.23-2.3 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF(1α), the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (60 μM) or nifedipine (1.4 μM), to the perfusion fluid abolished the effects of NPY to promote renal vasoconstriction and PG synthesis. Infusion of calmodulin inhibitors, trifluoperazine (2 μM), W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] (20 μM) or calmidazolium (0.2 μM), attenuated the renal vasoconstriction and the increase in PG output produced by NPY (0.7 nmol). In kidneys perfused with normal Tyrode's solution, infusion of NPY, in a concentration (1.7 x 10-8M) that produced only a small transient increase in renal vascular tone and failed to alter the renal output of PGs, enhanced the rise in PGE2 and 6-keto-PGF(1α) elicited by norepinephrine (0.25 nmol) but not by arginine vasopressin (0.004 nmol) or angiotensin II (0.09 nmol). The renal vasoconstriction elicited by norepinephrine and arginine vasopressin as well as by angiotensin II was enhanced by NPY. In kidneys perfused with Ca++-depleted Tyrode's solution norepinephrine-induced rise in perfusion pressure was abolished whereas PG output was reduced by 25 to 30{\%} and it was not altered by the infusion of NPY (1.7 x 10-8 M). These data suggest that NPY in large doses produces renal vasoconstriction and PG synthesis directly by a mechanism that depends primarily on extracellular Ca++ and calmodulin. However, small concentrations of NPY that are devoid of their direct effect on renal vascular tone and PG synthesis potentiates norepinephrine-induced component of PG synthesis that is dependent upon extracellular Ca++.",
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T1 - Neuropeptide Y stimulates renal prostaglandin synthesis in the isolated rat kidney

T2 - Contribution of Ca++ and calmodulin

AU - El-Din, M. M.M.

AU - Malik, Kafait

PY - 1988/1/1

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N2 - We have investigated the effects of neuropeptide Y (NPY) on vascular tone and renal output of prostaglandins (PGs) and the mechanism underlying these actions by examining the effects of Ca++ depletion, Ca++ channel blockers and calmodulin inhibitors in the isolated Tyrode's perfused rat kidney. Administration of NPY (0.23-2.3 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF(1α), the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (60 μM) or nifedipine (1.4 μM), to the perfusion fluid abolished the effects of NPY to promote renal vasoconstriction and PG synthesis. Infusion of calmodulin inhibitors, trifluoperazine (2 μM), W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] (20 μM) or calmidazolium (0.2 μM), attenuated the renal vasoconstriction and the increase in PG output produced by NPY (0.7 nmol). In kidneys perfused with normal Tyrode's solution, infusion of NPY, in a concentration (1.7 x 10-8M) that produced only a small transient increase in renal vascular tone and failed to alter the renal output of PGs, enhanced the rise in PGE2 and 6-keto-PGF(1α) elicited by norepinephrine (0.25 nmol) but not by arginine vasopressin (0.004 nmol) or angiotensin II (0.09 nmol). The renal vasoconstriction elicited by norepinephrine and arginine vasopressin as well as by angiotensin II was enhanced by NPY. In kidneys perfused with Ca++-depleted Tyrode's solution norepinephrine-induced rise in perfusion pressure was abolished whereas PG output was reduced by 25 to 30% and it was not altered by the infusion of NPY (1.7 x 10-8 M). These data suggest that NPY in large doses produces renal vasoconstriction and PG synthesis directly by a mechanism that depends primarily on extracellular Ca++ and calmodulin. However, small concentrations of NPY that are devoid of their direct effect on renal vascular tone and PG synthesis potentiates norepinephrine-induced component of PG synthesis that is dependent upon extracellular Ca++.

AB - We have investigated the effects of neuropeptide Y (NPY) on vascular tone and renal output of prostaglandins (PGs) and the mechanism underlying these actions by examining the effects of Ca++ depletion, Ca++ channel blockers and calmodulin inhibitors in the isolated Tyrode's perfused rat kidney. Administration of NPY (0.23-2.3 nmol) into the kidney produced a dose-related renal vasoconstriction and an increase in the output of PGE2 and 6-keto-PGF(1α), the stable hydrolysis product of PGI2. Omission of Ca++ (1.8 mM) or addition of Ca++ channel blockers, diltiazem (60 μM) or nifedipine (1.4 μM), to the perfusion fluid abolished the effects of NPY to promote renal vasoconstriction and PG synthesis. Infusion of calmodulin inhibitors, trifluoperazine (2 μM), W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide] (20 μM) or calmidazolium (0.2 μM), attenuated the renal vasoconstriction and the increase in PG output produced by NPY (0.7 nmol). In kidneys perfused with normal Tyrode's solution, infusion of NPY, in a concentration (1.7 x 10-8M) that produced only a small transient increase in renal vascular tone and failed to alter the renal output of PGs, enhanced the rise in PGE2 and 6-keto-PGF(1α) elicited by norepinephrine (0.25 nmol) but not by arginine vasopressin (0.004 nmol) or angiotensin II (0.09 nmol). The renal vasoconstriction elicited by norepinephrine and arginine vasopressin as well as by angiotensin II was enhanced by NPY. In kidneys perfused with Ca++-depleted Tyrode's solution norepinephrine-induced rise in perfusion pressure was abolished whereas PG output was reduced by 25 to 30% and it was not altered by the infusion of NPY (1.7 x 10-8 M). These data suggest that NPY in large doses produces renal vasoconstriction and PG synthesis directly by a mechanism that depends primarily on extracellular Ca++ and calmodulin. However, small concentrations of NPY that are devoid of their direct effect on renal vascular tone and PG synthesis potentiates norepinephrine-induced component of PG synthesis that is dependent upon extracellular Ca++.

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