Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in nucleus tractus solitarii of rats

L. K. Ho; K. Chen; I. C. Ho; Y. C. Shen; D. H.T. Yen; F. C.H. Li; Y. C. Lin; W. K. Kuo; Y. J. Lou; J. C. Yen

doi:10.1016/j.neuropharm.2008.06.024

Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in nucleus tractus solitarii of rats

L. K. Ho, K. Chen, I. C. Ho, Y. C. Shen, D. H.T. Yen, F. C.H. Li, Y. C. Lin, W. K. Kuo, Y. J. Lou, J. C. Yen^*

^*Corresponding author for this work

Department of Pharmacology

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Adrenomedullin (ADM), a 52-amino acid peptide, elicits differential cardiovascular responses when it is administered systemically or directly to the brain. We evaluated in the present study the hypothesis that ADM may modulate baroreceptor reflex (BRR) response through an ADM receptor-mediated cAMP/ protein kinase A (PKA)-dependent mechanism in the nucleus tractus solitarii (NTS), the terminal site for primary baroreceptor afferents, using Sprague-Dawley rats. Our immunoblot and immunohistochemical results showed that the two component proteins of the ADM₁ receptor complex, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)-2, were uniformly distributed and highly co-localized in the NTS. Site-specific microinjection of ADM (0.02-0.2 pmol) unilaterally into the NTS significantly increased BRR response and sensitivity in a time- and dose-related manner, without affecting arterial pressure and heart rate. The BRR enhancing effect of ADM was also temporally correlated with an up-regulation of PKA_β, the active form of PKA and an increase in PKA activity. In addition, the ADM-evoked BRR enhancement or PKA activation was abolished by co-microinjection with a selective ADM₁ receptor antagonist, ADM_22-52, an adenylyl cyclase inhibitor, SQ22536, or a PKA inhibitor, Rp-8-bromo-cAMP. These results suggest that ADM enhances BRR via activation of a cAMP/PKA-dependent mechanism by acting site-specifically on ADM₁ receptors in NTS.

Original language	English
Pages (from-to)	729-736
Number of pages	8
Journal	Neuropharmacology
Volume	55
Issue number	5
DOIs	https://doi.org/10.1016/j.neuropharm.2008.06.024
State	Published - Oct 2008

Keywords

Adrenomedullin
Baroreceptor reflex
Nucleus tractus solitarii
Protein kinase A
Rat

Access to Document

10.1016/j.neuropharm.2008.06.024

Cite this

@article{4075b68e76d14336a8cf849ae1751973,

title = "Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in nucleus tractus solitarii of rats",

abstract = "Adrenomedullin (ADM), a 52-amino acid peptide, elicits differential cardiovascular responses when it is administered systemically or directly to the brain. We evaluated in the present study the hypothesis that ADM may modulate baroreceptor reflex (BRR) response through an ADM receptor-mediated cAMP/ protein kinase A (PKA)-dependent mechanism in the nucleus tractus solitarii (NTS), the terminal site for primary baroreceptor afferents, using Sprague-Dawley rats. Our immunoblot and immunohistochemical results showed that the two component proteins of the ADM1 receptor complex, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)-2, were uniformly distributed and highly co-localized in the NTS. Site-specific microinjection of ADM (0.02-0.2 pmol) unilaterally into the NTS significantly increased BRR response and sensitivity in a time- and dose-related manner, without affecting arterial pressure and heart rate. The BRR enhancing effect of ADM was also temporally correlated with an up-regulation of PKAβ, the active form of PKA and an increase in PKA activity. In addition, the ADM-evoked BRR enhancement or PKA activation was abolished by co-microinjection with a selective ADM1 receptor antagonist, ADM22-52, an adenylyl cyclase inhibitor, SQ22536, or a PKA inhibitor, Rp-8-bromo-cAMP. These results suggest that ADM enhances BRR via activation of a cAMP/PKA-dependent mechanism by acting site-specifically on ADM1 receptors in NTS.",

keywords = "Adrenomedullin, Baroreceptor reflex, Nucleus tractus solitarii, Protein kinase A, Rat",

author = "Ho, {L. K.} and K. Chen and Ho, {I. C.} and Shen, {Y. C.} and Yen, {D. H.T.} and Li, {F. C.H.} and Lin, {Y. C.} and Kuo, {W. K.} and Lou, {Y. J.} and Yen, {J. C.}",

note = "Funding Information: This study was supported by a grant from Ministry of Education, Aim for the Top University Plan as well as research grants 95002-62-081 (J.C.Y.) from the Taipei City Hospital, V95E2-102 (L.K.H.) from Taipei Veterans General Hospital and NSC94-2314-B-010-045 (D.H.T.Y.) from the National Science Council, Taiwan, Republic of China. We thank Professor Samuel H.H. Chan, National Chair Professor of Neuroscience, National Sun Yat-Sen University, Taiwan, Republic of China, for his insightful suggestions on the design of this study and critical comments on the manuscript.",

year = "2008",

month = oct,

doi = "10.1016/j.neuropharm.2008.06.024",

language = "English",

volume = "55",

pages = "729--736",

journal = "Neuropharmacology",

issn = "0028-3908",

publisher = "Elsevier Ltd",

number = "5",

}

TY - JOUR

T1 - Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in nucleus tractus solitarii of rats

AU - Ho, L. K.

AU - Chen, K.

AU - Ho, I. C.

AU - Shen, Y. C.

AU - Yen, D. H.T.

AU - Li, F. C.H.

AU - Lin, Y. C.

AU - Kuo, W. K.

AU - Lou, Y. J.

AU - Yen, J. C.

N1 - Funding Information: This study was supported by a grant from Ministry of Education, Aim for the Top University Plan as well as research grants 95002-62-081 (J.C.Y.) from the Taipei City Hospital, V95E2-102 (L.K.H.) from Taipei Veterans General Hospital and NSC94-2314-B-010-045 (D.H.T.Y.) from the National Science Council, Taiwan, Republic of China. We thank Professor Samuel H.H. Chan, National Chair Professor of Neuroscience, National Sun Yat-Sen University, Taiwan, Republic of China, for his insightful suggestions on the design of this study and critical comments on the manuscript.

PY - 2008/10

Y1 - 2008/10

N2 - Adrenomedullin (ADM), a 52-amino acid peptide, elicits differential cardiovascular responses when it is administered systemically or directly to the brain. We evaluated in the present study the hypothesis that ADM may modulate baroreceptor reflex (BRR) response through an ADM receptor-mediated cAMP/ protein kinase A (PKA)-dependent mechanism in the nucleus tractus solitarii (NTS), the terminal site for primary baroreceptor afferents, using Sprague-Dawley rats. Our immunoblot and immunohistochemical results showed that the two component proteins of the ADM1 receptor complex, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)-2, were uniformly distributed and highly co-localized in the NTS. Site-specific microinjection of ADM (0.02-0.2 pmol) unilaterally into the NTS significantly increased BRR response and sensitivity in a time- and dose-related manner, without affecting arterial pressure and heart rate. The BRR enhancing effect of ADM was also temporally correlated with an up-regulation of PKAβ, the active form of PKA and an increase in PKA activity. In addition, the ADM-evoked BRR enhancement or PKA activation was abolished by co-microinjection with a selective ADM1 receptor antagonist, ADM22-52, an adenylyl cyclase inhibitor, SQ22536, or a PKA inhibitor, Rp-8-bromo-cAMP. These results suggest that ADM enhances BRR via activation of a cAMP/PKA-dependent mechanism by acting site-specifically on ADM1 receptors in NTS.

AB - Adrenomedullin (ADM), a 52-amino acid peptide, elicits differential cardiovascular responses when it is administered systemically or directly to the brain. We evaluated in the present study the hypothesis that ADM may modulate baroreceptor reflex (BRR) response through an ADM receptor-mediated cAMP/ protein kinase A (PKA)-dependent mechanism in the nucleus tractus solitarii (NTS), the terminal site for primary baroreceptor afferents, using Sprague-Dawley rats. Our immunoblot and immunohistochemical results showed that the two component proteins of the ADM1 receptor complex, calcitonin receptor-like receptor (CRLR) and receptor activity modifying protein (RAMP)-2, were uniformly distributed and highly co-localized in the NTS. Site-specific microinjection of ADM (0.02-0.2 pmol) unilaterally into the NTS significantly increased BRR response and sensitivity in a time- and dose-related manner, without affecting arterial pressure and heart rate. The BRR enhancing effect of ADM was also temporally correlated with an up-regulation of PKAβ, the active form of PKA and an increase in PKA activity. In addition, the ADM-evoked BRR enhancement or PKA activation was abolished by co-microinjection with a selective ADM1 receptor antagonist, ADM22-52, an adenylyl cyclase inhibitor, SQ22536, or a PKA inhibitor, Rp-8-bromo-cAMP. These results suggest that ADM enhances BRR via activation of a cAMP/PKA-dependent mechanism by acting site-specifically on ADM1 receptors in NTS.

KW - Adrenomedullin

KW - Baroreceptor reflex

KW - Nucleus tractus solitarii

KW - Protein kinase A

KW - Rat

UR - http://www.scopus.com/inward/record.url?scp=50849127821&partnerID=8YFLogxK

U2 - 10.1016/j.neuropharm.2008.06.024

DO - 10.1016/j.neuropharm.2008.06.024

M3 - Article

C2 - 18616957

AN - SCOPUS:50849127821

SN - 0028-3908

VL - 55

SP - 729

EP - 736

JO - Neuropharmacology

JF - Neuropharmacology

IS - 5

ER -

Adrenomedullin enhances baroreceptor reflex response via cAMP/PKA signaling in nucleus tractus solitarii of rats

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this