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Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat.

Li P, Sun HJ, Zhang LL, Ding L, Han Y, Zhu GQ, Zhou YB - PLoS ONE (2013)

Bottom Line: Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN.The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN.The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China ; Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT

Background and aim: Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats.

Methodology/principal findings: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin.

Conclusion: The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.

Show MeSH
The effect of PVN microinjection of saline, MTII (0.2 nmol), SHU9119 (0.4 nmol) or HS024 (1.0 nmol) on the adipose afferent reflex (AAR) and the effect of PVN microinjection of MTII on the AAR after pretreatment with SHU9119 or HS024.MTII was administered 8 min after the microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024. The AAR was evaluated by the RSNA and MAP responses to capsaicin application in the inguinal white adipose tissue (iWAT). Values are Mean±SE. *P<0.05 compared with Saline. †P<0.05 compared with MTII. n=6 for each group.
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pone-0080295-g004: The effect of PVN microinjection of saline, MTII (0.2 nmol), SHU9119 (0.4 nmol) or HS024 (1.0 nmol) on the adipose afferent reflex (AAR) and the effect of PVN microinjection of MTII on the AAR after pretreatment with SHU9119 or HS024.MTII was administered 8 min after the microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024. The AAR was evaluated by the RSNA and MAP responses to capsaicin application in the inguinal white adipose tissue (iWAT). Values are Mean±SE. *P<0.05 compared with Saline. †P<0.05 compared with MTII. n=6 for each group.

Mentions: Microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024 for 8 min significantly attenuated the AAR. Pretreatment with SHU9119 abolished the AAR enhancement response to MTII. MC4R antagonist HS024 almost produced the same effects as the MC3/4R antagonist SHU9119 (Figure 4). The representative recording showed that pretreatment with HS024 (1.0 nmol) abolished the AAR enhancement responses to MTII (Figure 3c).


Melanocortin 4 receptors in the paraventricular nucleus modulate the adipose afferent reflex in rat.

Li P, Sun HJ, Zhang LL, Ding L, Han Y, Zhu GQ, Zhou YB - PLoS ONE (2013)

The effect of PVN microinjection of saline, MTII (0.2 nmol), SHU9119 (0.4 nmol) or HS024 (1.0 nmol) on the adipose afferent reflex (AAR) and the effect of PVN microinjection of MTII on the AAR after pretreatment with SHU9119 or HS024.MTII was administered 8 min after the microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024. The AAR was evaluated by the RSNA and MAP responses to capsaicin application in the inguinal white adipose tissue (iWAT). Values are Mean±SE. *P<0.05 compared with Saline. †P<0.05 compared with MTII. n=6 for each group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3823614&req=5

pone-0080295-g004: The effect of PVN microinjection of saline, MTII (0.2 nmol), SHU9119 (0.4 nmol) or HS024 (1.0 nmol) on the adipose afferent reflex (AAR) and the effect of PVN microinjection of MTII on the AAR after pretreatment with SHU9119 or HS024.MTII was administered 8 min after the microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024. The AAR was evaluated by the RSNA and MAP responses to capsaicin application in the inguinal white adipose tissue (iWAT). Values are Mean±SE. *P<0.05 compared with Saline. †P<0.05 compared with MTII. n=6 for each group.
Mentions: Microinjection of the MC3/4R antagonist SHU9119 or MC4R antagonist HS024 for 8 min significantly attenuated the AAR. Pretreatment with SHU9119 abolished the AAR enhancement response to MTII. MC4R antagonist HS024 almost produced the same effects as the MC3/4R antagonist SHU9119 (Figure 4). The representative recording showed that pretreatment with HS024 (1.0 nmol) abolished the AAR enhancement responses to MTII (Figure 3c).

Bottom Line: Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN.The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN.The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.

View Article: PubMed Central - PubMed

Affiliation: Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, China ; Department of Cardiology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT

Background and aim: Paraventricular nucleus (PVN) of hypothalamus is an important central component in modulating adipose afferent reflex (AAR). Melanocortin receptors (MC3/4Rs) expressions are found in the hypothalamic PVN. This study was designed to determine the roles of MC3/4Rs in the PVN in modulating the AAR and its downstream signaling pathway in normal rats.

Methodology/principal findings: Renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in anaesthetized rats. AAR was evaluated using RSNA and MAP responses to capsaicin injection into the inguinal white adipose tissue (iWAT). Microinjection of the MC3/4R agonist melanotan II (MTII) into the PVN enhanced the AAR. The MC3/4R antagonist SHU9119 or MC4R antagonist HS024 attenuated the AAR and abolished MTII-induced AAR response. The adenylate cyclase (AC) inhibitor SQ22536 or the protein kinase A (PKA) inhibitor Rp-cAMP attenuated the AAR and the effect of MTII on the AAR was abolished by pretreatment with SQ22536 or Rp-cAMP in the PVN. Furthermore, both PVN microinjection of MTII and iWAT injection of capsaicin increased the cAMP level in the PVN. SHU9119 in the PVN abolished the increase in cAMP level which induced by iWAT injection of capsaicin.

Conclusion: The activation of MC4Rs rather than MC3Rs enhances the AAR, and a cAMP-PKA pathway is involved in the effects of MC4Rs in the PVN.

Show MeSH