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PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice

The two sister peptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) and their receptors, the PAC1 –and the VPAC2 receptors, are involved in regulation of the circadian timing system. PACAP as a neurotransmitter in the retinohypothalamic tra...

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Autores principales: Hannibal, Jens, Georg, Birgitte, Fahrenkrug, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695784/
https://www.ncbi.nlm.nih.gov/pubmed/29155851
http://dx.doi.org/10.1371/journal.pone.0188166
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author Hannibal, Jens
Georg, Birgitte
Fahrenkrug, Jan
author_facet Hannibal, Jens
Georg, Birgitte
Fahrenkrug, Jan
author_sort Hannibal, Jens
collection PubMed
description The two sister peptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) and their receptors, the PAC1 –and the VPAC2 receptors, are involved in regulation of the circadian timing system. PACAP as a neurotransmitter in the retinohypothalamic tract (RHT) and VIP as a neurotransmitter, involved in synchronization of SCN neurons. Behavior and physiology in VPAC2 deficient mice are strongly regulated by light most likely as a result of masking. Consequently, we used VPAC2 and PAC1/VPAC2 double mutant mice in comparison with PAC1 receptor deficient mice to further elucidate the role of PACAP in the light mediated regulation of behavior and physiology of the circadian system. We compared circadian rhythms in mice equipped with running wheels or implanted radio-transmitter measuring core body temperature kept in a full photoperiod ((FPP)(12:12 h light dark-cycles (LD)) and skeleton photo periods (SPP) at high and low light intensity. Furthermore, we examined the expression of PAC1- and VPAC2 receptors in the SCN of the different genotypes in combination with visualization of PACAP and VIP and determined whether compensatory changes in peptide and/or receptor expression in the reciprocal knockouts (KO) (PAC1 and VPAC2) had occurred. Our data demonstrate that in although being closely related at both ligand and receptor structure/sequence, PACAP/PAC1 receptor signaling are independent of VIP/VPAC2 receptor signaling and vice versa. Furthermore, lack of either of the receptors does not result in compensatory changes at neither the physiological or anatomical level. PACAP/PAC1 signaling is important for light regulated behavior, VIP/VPAC2signaling for stable clock function and both signaling pathways may play a role in shaping diurnality versus nocturnality.
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spelling pubmed-56957842017-11-30 PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice Hannibal, Jens Georg, Birgitte Fahrenkrug, Jan PLoS One Research Article The two sister peptides, pituitary adenylate cyclase activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) and their receptors, the PAC1 –and the VPAC2 receptors, are involved in regulation of the circadian timing system. PACAP as a neurotransmitter in the retinohypothalamic tract (RHT) and VIP as a neurotransmitter, involved in synchronization of SCN neurons. Behavior and physiology in VPAC2 deficient mice are strongly regulated by light most likely as a result of masking. Consequently, we used VPAC2 and PAC1/VPAC2 double mutant mice in comparison with PAC1 receptor deficient mice to further elucidate the role of PACAP in the light mediated regulation of behavior and physiology of the circadian system. We compared circadian rhythms in mice equipped with running wheels or implanted radio-transmitter measuring core body temperature kept in a full photoperiod ((FPP)(12:12 h light dark-cycles (LD)) and skeleton photo periods (SPP) at high and low light intensity. Furthermore, we examined the expression of PAC1- and VPAC2 receptors in the SCN of the different genotypes in combination with visualization of PACAP and VIP and determined whether compensatory changes in peptide and/or receptor expression in the reciprocal knockouts (KO) (PAC1 and VPAC2) had occurred. Our data demonstrate that in although being closely related at both ligand and receptor structure/sequence, PACAP/PAC1 receptor signaling are independent of VIP/VPAC2 receptor signaling and vice versa. Furthermore, lack of either of the receptors does not result in compensatory changes at neither the physiological or anatomical level. PACAP/PAC1 signaling is important for light regulated behavior, VIP/VPAC2signaling for stable clock function and both signaling pathways may play a role in shaping diurnality versus nocturnality. Public Library of Science 2017-11-20 /pmc/articles/PMC5695784/ /pubmed/29155851 http://dx.doi.org/10.1371/journal.pone.0188166 Text en © 2017 Hannibal et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hannibal, Jens
Georg, Birgitte
Fahrenkrug, Jan
PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title_full PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title_fullStr PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title_full_unstemmed PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title_short PAC1- and VPAC2 receptors in light regulated behavior and physiology: Studies in single and double mutant mice
title_sort pac1- and vpac2 receptors in light regulated behavior and physiology: studies in single and double mutant mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5695784/
https://www.ncbi.nlm.nih.gov/pubmed/29155851
http://dx.doi.org/10.1371/journal.pone.0188166
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