Modulatory role of adenylyl cyclase and protein kinase A (PKA) in 5-hydroxytriptamines3 induced intracellular calcium increase in parasympathetic neurons of rat major pelvic ganglia

Dae Ran Kim, Seung Kyu Cha, Kyu Sang Park, Eun Seop Song, Young Ho Park, Yun Seob Song, In Deok Kong

Research output: Contribution to journalArticle

Abstract

Purpose: Serotonin has effects on the bladder contraction or urethral sphincter tone. Different subtypes of 5-hydroxytriptamine (5-HT) receptors appear to mediate the effects of serotonin on voiding. 5-HT1 and 5-HT2, metamorphic receptors, are examined well. However 5-HT3, ionotrophic receptors, are not examined well. Pelvic ganglia provide the majority of the innervation of the lower urinary tract. Major pelvic ganglia (MPG) in rats are autonomic ganglia, containing both sympathetic and parasympathetic neurons related with voiding. We examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) in 5-HT3 induced intra cellular calcium increase in rat MPG. Materials and methods: The regulatory effects by AC and PKA were investigated in a single neuron of male rat major pelvic ganglia using patch clamp and fluorescence Ca2+ measurement techniques. Results: Inward currents were induced by 5-HT (10 μM) at only parasympathetic neurons of MPG. MDL7222 (10-6 M), selective 5-HT3 receptor antagonists, completely abolished the 5-HT induced inward currents. 5-HT (10 μM) induced intracelluar increases of calcium. These increases were blocked by an AC inhibitor SQ22536 (2×10-5 M) and myristoylated PKA inhibitor (10-7 M). Furthermore, foskolin (10-6M), AC activator, augmented the 5-HT induced intracellular calcium increase. Conclusions: The activation of AC/PKA-dependent pathway could enhance 5-HT3 induced intacellular calcium increase in parasympathetic neurons of rat MPG and these is helpful for the better understanding the mechanisms of the bladder contraction or urethral sphincter tone.

Original languageEnglish
Pages (from-to)541-547
Number of pages7
JournalKorean Journal of Urology
Volume47
Issue number5
DOIs
Publication statusPublished - 2006 May

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Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Ganglia
Calcium
Neurons
Receptors, Serotonin, 5-HT3
Urethra
Urinary Bladder
Autonomic Ganglia
Serotonin Agents
Serotonin 5-HT3 Receptor Antagonists
Protein Kinase Inhibitors
Urinary Tract
Serotonin
Fluorescence

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

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title = "Modulatory role of adenylyl cyclase and protein kinase A (PKA) in 5-hydroxytriptamines3 induced intracellular calcium increase in parasympathetic neurons of rat major pelvic ganglia",
abstract = "Purpose: Serotonin has effects on the bladder contraction or urethral sphincter tone. Different subtypes of 5-hydroxytriptamine (5-HT) receptors appear to mediate the effects of serotonin on voiding. 5-HT1 and 5-HT2, metamorphic receptors, are examined well. However 5-HT3, ionotrophic receptors, are not examined well. Pelvic ganglia provide the majority of the innervation of the lower urinary tract. Major pelvic ganglia (MPG) in rats are autonomic ganglia, containing both sympathetic and parasympathetic neurons related with voiding. We examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) in 5-HT3 induced intra cellular calcium increase in rat MPG. Materials and methods: The regulatory effects by AC and PKA were investigated in a single neuron of male rat major pelvic ganglia using patch clamp and fluorescence Ca2+ measurement techniques. Results: Inward currents were induced by 5-HT (10 μM) at only parasympathetic neurons of MPG. MDL7222 (10-6 M), selective 5-HT3 receptor antagonists, completely abolished the 5-HT induced inward currents. 5-HT (10 μM) induced intracelluar increases of calcium. These increases were blocked by an AC inhibitor SQ22536 (2×10-5 M) and myristoylated PKA inhibitor (10-7 M). Furthermore, foskolin (10-6M), AC activator, augmented the 5-HT induced intracellular calcium increase. Conclusions: The activation of AC/PKA-dependent pathway could enhance 5-HT3 induced intacellular calcium increase in parasympathetic neurons of rat MPG and these is helpful for the better understanding the mechanisms of the bladder contraction or urethral sphincter tone.",
author = "Kim, {Dae Ran} and Cha, {Seung Kyu} and Park, {Kyu Sang} and Song, {Eun Seop} and Park, {Young Ho} and Song, {Yun Seob} and Kong, {In Deok}",
year = "2006",
month = "5",
doi = "10.4111/kju.2006.47.5.541",
language = "English",
volume = "47",
pages = "541--547",
journal = "Korean Journal of Urology",
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T1 - Modulatory role of adenylyl cyclase and protein kinase A (PKA) in 5-hydroxytriptamines3 induced intracellular calcium increase in parasympathetic neurons of rat major pelvic ganglia

AU - Kim, Dae Ran

AU - Cha, Seung Kyu

AU - Park, Kyu Sang

AU - Song, Eun Seop

AU - Park, Young Ho

AU - Song, Yun Seob

AU - Kong, In Deok

PY - 2006/5

Y1 - 2006/5

N2 - Purpose: Serotonin has effects on the bladder contraction or urethral sphincter tone. Different subtypes of 5-hydroxytriptamine (5-HT) receptors appear to mediate the effects of serotonin on voiding. 5-HT1 and 5-HT2, metamorphic receptors, are examined well. However 5-HT3, ionotrophic receptors, are not examined well. Pelvic ganglia provide the majority of the innervation of the lower urinary tract. Major pelvic ganglia (MPG) in rats are autonomic ganglia, containing both sympathetic and parasympathetic neurons related with voiding. We examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) in 5-HT3 induced intra cellular calcium increase in rat MPG. Materials and methods: The regulatory effects by AC and PKA were investigated in a single neuron of male rat major pelvic ganglia using patch clamp and fluorescence Ca2+ measurement techniques. Results: Inward currents were induced by 5-HT (10 μM) at only parasympathetic neurons of MPG. MDL7222 (10-6 M), selective 5-HT3 receptor antagonists, completely abolished the 5-HT induced inward currents. 5-HT (10 μM) induced intracelluar increases of calcium. These increases were blocked by an AC inhibitor SQ22536 (2×10-5 M) and myristoylated PKA inhibitor (10-7 M). Furthermore, foskolin (10-6M), AC activator, augmented the 5-HT induced intracellular calcium increase. Conclusions: The activation of AC/PKA-dependent pathway could enhance 5-HT3 induced intacellular calcium increase in parasympathetic neurons of rat MPG and these is helpful for the better understanding the mechanisms of the bladder contraction or urethral sphincter tone.

AB - Purpose: Serotonin has effects on the bladder contraction or urethral sphincter tone. Different subtypes of 5-hydroxytriptamine (5-HT) receptors appear to mediate the effects of serotonin on voiding. 5-HT1 and 5-HT2, metamorphic receptors, are examined well. However 5-HT3, ionotrophic receptors, are not examined well. Pelvic ganglia provide the majority of the innervation of the lower urinary tract. Major pelvic ganglia (MPG) in rats are autonomic ganglia, containing both sympathetic and parasympathetic neurons related with voiding. We examined the modulatory role of adenylyl cyclase (AC) and protein kinase A (PKA) in 5-HT3 induced intra cellular calcium increase in rat MPG. Materials and methods: The regulatory effects by AC and PKA were investigated in a single neuron of male rat major pelvic ganglia using patch clamp and fluorescence Ca2+ measurement techniques. Results: Inward currents were induced by 5-HT (10 μM) at only parasympathetic neurons of MPG. MDL7222 (10-6 M), selective 5-HT3 receptor antagonists, completely abolished the 5-HT induced inward currents. 5-HT (10 μM) induced intracelluar increases of calcium. These increases were blocked by an AC inhibitor SQ22536 (2×10-5 M) and myristoylated PKA inhibitor (10-7 M). Furthermore, foskolin (10-6M), AC activator, augmented the 5-HT induced intracellular calcium increase. Conclusions: The activation of AC/PKA-dependent pathway could enhance 5-HT3 induced intacellular calcium increase in parasympathetic neurons of rat MPG and these is helpful for the better understanding the mechanisms of the bladder contraction or urethral sphincter tone.

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