Spatial association of prolyl oligopeptidase, inositol 1,4,5-triphosphate type 1 receptor, substance P and its neurokinin-1 receptor in the rat brain: An immunohistochemical colocalization study

• Published in: Neuroscience Vol. 153; no. 4; pp. 1177 - 1189
• Main Authors: Myohanen, T T, Venalainen, JI, Garcia-Horsman, JA, Mannisto, P T
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 02.06.2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - anatomy & histology; Brain - metabolism; Calcium Channels - metabolism; Fundamental and applied biological sciences. Psychology; Inositol 1,4,5-Trisphosphate Receptors; long-term potentiation; Male; memory and learning; Neurology; neuropeptides; protein degradation; Rats; Rats, Wistar; Receptors, Cytoplasmic and Nuclear - metabolism; Receptors, Neurokinin-1 - metabolism; serine endopeptidase; Serine Endopeptidases - metabolism; Substance P - metabolism; thalamocortical signaling; Vertebrates: nervous system and sense organs; prolyl oligopeptidase; VPA; neuropeptides; LTP; phosphate buffer; thalamocortical signaling; IP 3R1; DPPIV; inositol 1,4,5-triphosphate receptor type 1; IP 3; dipeptidyl peptidase IV; inositol 1,4,5-triphosphate; substance P; SP; long-term depression; neurokinin-1 receptor (substance P receptor); serine endopeptidase; POP; valproate; PB; memory and learning; NK-1R; LTD; protein degradation; long-term potentiation; IP3R1; IP3; Immunohistochemistry; Rat; Memory; Central nervous system; Prolyl oligopeptidase; Neuropeptide; Encephalon; Learning; Acquisition process; Synaptic plasticity; Biological receptor; Inositol; NK1 Tachykinin receptor; Serine endopeptidases; Enzyme; Substance P; Rodentia; Peptidases; Vertebrata; Mammalia; Animal; Hydrolases; Tachykinin
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.02.047

Abstract Prolyl oligopeptidase (POP) is a serine endopeptidase which hydrolyzes proline-containing peptides shorter than 30 amino acids. It has been suggested that POP is associated with cognitive functions, possibly via the cleavage of neuropeptides such as substance P (SP). Recently, several studies have also linked POP to the inositol 1,4,5-triphosphate (IP3 ) signaling. However, the neuroanatomical interactions between these substances are not known. We used double-labeled immunofluorescence to determine the POP colocalization with SP, SP receptor (neurokinin-1 receptor, NK-1R) and IP3 type 1 receptor (IP3 R1) in the rat brain. Furthermore, since striatal and cortical GABAergic neurons are involved in SP neurotransmission, we studied the coexpression of POP, SP and GABA by triple-labeled immunofluorescence. POP was moderately present in IP3 R1-containing cells in cortex; the colocalization was particularly high in the thalamus, hippocampal CA1 field and cerebellar Purkinje cells. Colocalization of POP with SP and NK1-receptor was infrequent throughout the brain, though some POP and SP coexpression was observed in cerebellar Purkinje cells. We also found that POP partially colocalized with SP-containing GABAergic neurons in striatum and cortex. Our findings support the view that POP is at least spatially associated with the IP3 -signaling in the thalamus, hippocampus and cerebellar Purkinje cells. This might point to a role for POP in the regulation of long-term potentiation and/or depression. Moreover, the low degree of colocalization of POP, SP and its NK-1R suggests that a transport system is needed either for POP or SP to make hydrolysis possible and that POP may act both intra- and extracellularly.