Distribution of cGMP-DEPENDENT protein kinase type I and its isoforms in the mouse brain and retina

被引:51
作者
Feil, S [1 ]
Zimmermann, P [1 ]
Knorn, A [1 ]
Brummer, S [1 ]
Schlossmann, J [1 ]
Hofmann, F [1 ]
Feil, R [1 ]
机构
[1] Tech Univ Munich, Inst Pharmakol & Toxikol, D-80802 Munich, Germany
关键词
brain; cGMP; immunohistochemistry; nitric oxide; protein kinase; retina;
D O I
10.1016/j.neuroscience.2005.06.051
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Nitric oxide (NO) modulates a variety of processes in the mammalian brain, but the mechanisms of neuronal NO signaling are poorly understood. In the periphery, many effects of NO are mediated via the generation of the second messenger cyclic guanosine-3',5'-monophosphate (cGMP) and activation of the cGMP-dependent protein kinase type I (cGKI). However, previous studies suggested that the expression of cGKI in the nervous system is rather restricted, thus, questioning the functional significance of the cGMP/cGKI pathway as a mediator of NO signaling in the brain. Here we have performed a detailed immunohistochemical study to elucidate the distribution of cGKI in the CNS and eye of the mouse. Expression of cGKI protein was detected not only in the previously described areas (cerebellum, hippocampus, dorsomedial hypothalamus) but also in a number of additional regions, such as medulla, subcommissural organ, cerebral cortex, amygdala, habenulae, various hypothalamic regions, olfactory bulb, pituitary gland, and retina. Immunoblotting with isoform-specific antibodies indicated that the cGKI alpha isoform is prominent in the cerebellum and medulla, whereas the cGKI beta isoform is predominant in the cortex, hippocampus, hypothalamus, and olfactory bulb. Similar levels of the isoforms were detected in the pituitary gland and eye. Thus, it appears that distinct brain regions express distinct cGKI isoforms that signal via distinct pathways. Together, these results improve our understanding of the cellular and molecular mechanisms of NO/ cGMP/cGKI signaling and indicate that the distribution and functional relevance of this pathway in the mammalian brain is broader than previously thought. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:863 / 868
页数:6
相关论文
共 21 条
[1]   Presynaptic role of cGMP-dependent protein kinase during long-lasting potentiation [J].
Arancio, O ;
Antonova, I ;
Gambaryan, S ;
Lohmann, SM ;
Wood, JS ;
Lawrence, DS ;
Hawkins, RD .
JOURNAL OF NEUROSCIENCE, 2001, 21 (01) :143-149
[2]   The dorsomedial hypothalamic nucleus and its role in ingestive behavior and body weight regulation: Lessons learned from lesioning studies [J].
Bellinger, LL ;
Bernardis, LL .
PHYSIOLOGY & BEHAVIOR, 2002, 76 (03) :431-442
[3]   Distribution of nitric oxide synthase and nitric oxide-receptive, cyclic GMP-producing structures in the rat brain [J].
De Vente, J ;
Hopkins, DA ;
Markerink-Van Ittersum, M ;
Emson, PC ;
Schmidt, HHHW ;
Steinbusch, HWM .
NEUROSCIENCE, 1998, 87 (01) :207-241
[4]   Localization of the cGMP-dependent protein kinases in relation to nitric oxide synthase in the brain [J].
El-Husseini, AED ;
Williams, J ;
Reiner, PB ;
Pelech, S ;
Vincent, SR .
JOURNAL OF CHEMICAL NEUROANATOMY, 1999, 17 (01) :45-55
[5]  
Feil R, 2005, REV NEUROSCIENCE, V16, P23
[6]   Impairment of LTD and cerebellar learning by Purkinje cell-specific ablation of cGMP-dependent protein kinase I [J].
Feil, R ;
Hartmann, J ;
Luo, CD ;
Wolfsgruber, W ;
Schilling, K ;
Feil, S ;
Barski, JJ ;
Meyer, M ;
Konnerth, A ;
De Zeeuw, CI ;
Hofmann, F .
JOURNAL OF CELL BIOLOGY, 2003, 163 (02) :295-302
[7]   Functional reconstitution of vascular smooth muscle cells with cGMP-dependent protein kinase I isoforms [J].
Feil, R ;
Gappa, N ;
Rutz, M ;
Schlossmann, J ;
Rose, CR ;
Konnerth, A ;
Brummer, S ;
Kühbandner, S ;
Hofmann, F .
CIRCULATION RESEARCH, 2002, 90 (10) :1080-1086
[8]   FUNCTIONAL CGMP-DEPENDENT PROTEIN-KINASE IS PHOSPHORYLATED IN ITS CATALYTIC DOMAIN AT THREONINE-516 [J].
FEIL, R ;
KELLERMANN, J ;
HOFMANN, F .
BIOCHEMISTRY, 1995, 34 (40) :13152-13158
[9]  
Gamm DM, 2000, INVEST OPHTH VIS SCI, V41, P2766
[10]   Distribution of IRAG and cGKI-isoforms in murine tissues [J].
Geiselhöringer, A ;
Gaisa, A ;
Hofmann, F ;
Schlossmann, J .
FEBS LETTERS, 2004, 575 (1-3) :19-22