Genetic inactivation of prohormone convertase (PC1) causes a reduction in cholecystokinin (CCK) levels in the hippocampus, amygdala, pons and medulla in mouse brain that correlates with the degree of colocalization of PC1 and CCK mRNA in these structures in rat brain.
Prohormone convertase (PC1) is found in endocrine cell lines that express cholecystokinin (CCK) mRNA and process pro CCK to biologically active products. Other studies have demonstrated that PC1 may be a one of the enzymes responsible for the endoproteolytic cleavages that occur in pro CCK during its biosynthesis and processing. Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain. A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA. CCK levels were measured in PC1 knockout and control mice to assess the degree to which loss of PC1 changed CCK content. CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls. These results are highly correlated with the colocalization of CCK and PC1. The majority of CCK mRNA-positive neurons in the pyramidal cell layer of the hippocampus express PC1 mRNA and greater than 50% of CCK mRNA-positive neurons in several nuclei of the amygdala also express PC1. These results demonstrate that PC1 is important for CCK processing. PC2 and PC5 are also widely colocalized with CCK. It may be that PC2, PC5 or another non-PC enzyme are able to substitute for PC1 and sustain production of some amidated CCK. Together these enzymes may represent a redundant system to insure the production of CCK.
Cain
B M
BM
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Connolly
K
K
Blum
A C
AC
Vishnuvardhan
D
D
Marchand
J E
JE
Zhu
X
X
Steiner
D F
DF
Beinfeld
M C
MC
D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D011149:Pons / Q000378:metabolism; D043484:Proprotein Convertases / Q000172:deficiency / Q000235:genetics*; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats
D012333:RNA, Messenger; D002766:Cholecystokinin; D043484:Proprotein Convertases