The Role of Cobalamin in the Central and Peripheral Nervous Systems: Mechanistic Insights

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms, PACAP-38 and PACAP-27, and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems, with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

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The PACAP/PAC1 Receptor System and Feeding

Brain Sciences ◽

10.3390/brainsci12010013 ◽

2021 ◽

Vol 12 (1) ◽

pp. 13

Author(s):

Keerthana Sureshkumar ◽

Andrea Saenz ◽

Syed M. Ahmad ◽

Kabirullah Lutfy

Keyword(s):

Food Intake ◽

Energy Homeostasis ◽

Brain Regions ◽

Regulatory Action ◽

Laboratory Animals ◽

Pac1 Receptor ◽

Receptor System ◽

Nervous Systems ◽

Peripheral Nervous Systems

Pituitary adenylyl cyclase activating polypeptide (PACAP) belongs to the vasoactive intestinal polypeptide (VIP)/secretin/glucagon superfamily. PACAP is present in two forms (PACAP-38 and PACAP-27) and binds to three guanine-regulatory (G) protein-coupled receptors (PAC1, VPAC1, and VPAC2). PACAP is expressed in the central and peripheral nervous systems, with high PACAP levels found in the hypothalamus, a brain region involved in feeding and energy homeostasis. PAC1 receptors are high-affinity and PACAP-selective receptors, while VPAC1 and VPAC2 receptors show a comparable affinity to PACAP and VIP. PACAP and its receptors are expressed in the central and peripheral nervous systems with moderate to high expression in the hypothalamus, amygdala, and other limbic structures. Consistent with their expression, PACAP is involved in several physiological responses and pathological states. A growing body of literature suggests that PACAP regulates food intake in laboratory animals. However, there is no comprehensive review of the literature on this topic. Thus, the purpose of this article is to review the literature regarding the role of PACAP and its receptors in food intake regulation and to synthesize how PACAP exerts its anorexic effects in different brain regions. To achieve this goal, we searched PubMed and reviewed 68 articles regarding the regulatory action of PACAP on food intake. Here, we present the literature regarding the effect of exogenous PACAP on feeding and the role of endogenous PACAP in this process. We also provide evidence regarding the effect of PACAP on the homeostatic and hedonic aspects of food intake, the neuroanatomical sites where PACAP exerts its regulatory action, which PACAP receptors may be involved, and the role of various signaling pathways and neurotransmitters in hypophagic effects of PACAP.

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THE ROLE OF RET RECEPTOR TYROSINE KINASE AND GLIAL DERIVED NEUROTROPHlC FACTOR IN DEVELOPMENT OF THE EXCRETORY AND PERIPHERAL NERVOUS SYSTEMS

Epithelial Morphogenesis in Development and Disease ◽

10.1201/b20586-22 ◽

2003 ◽

pp. 256-272

Keyword(s):

Tyrosine Kinase ◽

Receptor Tyrosine Kinase ◽

Nervous Systems ◽

Peripheral Nervous Systems

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Section Review: Central & Peripheral Nervous Systems: Disorders of sexual response: Pioneering new pharmaceutical and therapeutic opportunities

Expert Opinion on Investigational Drugs ◽

10.1517/13543784.4.7.621 ◽

1995 ◽

Vol 4 (7) ◽

pp. 621-636 ◽

Cited By ~ 2

Author(s):

Mark M. Foreman

Keyword(s):

Sexual Response ◽

Nervous Systems ◽

Peripheral Nervous Systems

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Synapsin I (protein I), a nerve terminal-specific phosphoprotein. I. Its general distribution in synapses of the central and peripheral nervous system demonstrated by immunofluorescence in frozen and plastic sections.

The Journal of Cell Biology ◽

10.1083/jcb.96.5.1337 ◽

1983 ◽

Vol 96 (5) ◽

pp. 1337-1354 ◽

Cited By ~ 345

Author(s):

P De Camilli ◽

R Cameron ◽

P Greengard

Keyword(s):

Nervous System ◽

Detailed Examination ◽

Specific Protein ◽

Nerve Cells ◽

General Distribution ◽

Synapsin I ◽

Nervous Systems ◽

Synaptic Region ◽

Specific Localization ◽

Peripheral Nervous Systems

Synapsin I (formerly referred to as protein I) is the collective name for two almost identical phosphoproteins, synapsin Ia and synapsin Ib (protein Ia and protein Ib), present in the nervous system. Synapsin I has previously been shown by immunoperoxidase studies (De Camilli, P., T. Ueda, F. E. Bloom, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA, 76:5977-5981; Bloom, F. E., T. Ueda, E. Battenberg, and P. Greengard, 1979, Proc. Natl. Acad. Sci. USA 76:5982-5986) to be a neuron-specific protein, present in both the central and peripheral nervous systems and concentrated in the synaptic region of nerve cells. In those preliminary studies, the occurrence of synapsin I could be demonstrated in only a portion of synapses. We have now carried out a detailed examination of the distribution of synapsin I immunoreactivity in the central and peripheral nervous systems. In this study we have attempted to maximize the level of resolution of immunohistochemical light microscopy images in order to estimate the proportion of immunoreactive synapses and to establish their precise distribution. Optimal results were obtained by the use of immunofluorescence in semithin sections (approximately 1 micron) prepared from Epon-embedded nonosmicated tissues after the Epon had been removed. Our results confirm the previous observations on the specific localization of synapsin I in nerve cells and synapses. In addition, the results strongly suggest that, with a few possible exceptions involving highly specialized neurons, all synapses contain synapsin I. Finally, immunocytochemical experiments indicate that synapsin I appearance in the various regions of the developing nervous system correlates topographically and temporally with the appearance of synapses. In two accompanying papers (De Camilli, P., S. M. Harris, Jr., W. B. Huttner, and P. Greengard, and Huttner, W. B., W. Schiebler, P. Greengard, and P. De Camilli, 1983, J. Cell Biol. 96:1355-1373 and 1374-1388, respectively), evidence is presented that synapsin I is specifically associated with synaptic vesicles in nerve endings.

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