Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration.
CCK and apolipoprotein AIV (apo AIV) are gastrointestinal satiety signals whose synthesis and secretion by the gut are stimulated by fat absorption. Intraperitoneally administered CCK-8 is more potent in suppressing food intake than a similar dose administered intravenously, but the reason for this disparity is unclear. In contrast, both intravenous and intraperitoneally administered apo AIV are equally as potent in inhibiting food intake. When we compared the lymphatic concentration of CCK-8 and apo AIV, we found that neither intraperitoneally nor intravenously administered CCK-8 or apo AIV altered lymphatic flow rate. Interestingly, intraperitoneal administration of CCK-8 produced a significantly higher lymphatic concentration at 15 min than did intravenous administration. Intraperitoneal injection of apo AIV also yielded a higher lymphatic concentration at 30 min than did intravenous administration. Intraperitoneal administration of CCK-8 and apo AIV also resulted in a much longer period of elevated CCK-8 and apo AIV peptide concentration in lymph than intravenous administration. Furthermore, enzymatic activity of dipeptidyl peptidase IV (DPPIV) and aminopeptidase was higher in plasma than in lymph during fasting, and so, satiation peptides, such as CCK-8 and apo AIV in the lymph, are protected from degradation by the significantly lower DPPIV and aminopeptidase activity levels in lymph than in plasma. Therefore, the higher potency of intraperitoneally administered CCK-8 compared with intravenously administered CCK-8 in inhibiting food intake may be explained by both its higher concentration in lymph and the prolonged duration of its presence in the lamina propria.
Lo
Chun-Min
CM
Cincinnati Obesity Research Center, University of Cincinnati College of Medicine, Cincinnati, Ohio 45237, USA.
Xu
Min
M
Yang
Qing
Q
Zheng
Shuqin
S
Carey
Katherine M
KM
Tubb
Matthew R
MR
Davidson
W Sean
WS
Liu
Min
M
Woods
Stephen C
SC
Tso
Patrick
P
D000626:Aminopeptidases / Q000097:blood; D000818:Animals; D001054:Apolipoproteins A / Q000008:administration & dosage* / Q000378:metabolism; D001067:Appetite Depressants / Q000008:administration & dosage* / Q000378:metabolism; D002766:Cholecystokinin / Q000008:administration & dosage* / Q000378:metabolism; D018819:Dipeptidyl Peptidase 4 / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008196:Lymph / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors
D001054:Apolipoproteins A; D001067:Appetite Depressants; D010446:Peptide Fragments; D011994:Recombinant Proteins; C022205:apolipoprotein A-IV; C410885:cholecystokinin 8; D002766:Cholecystokinin; D000626:Aminopeptidases; D018819:Dipeptidyl Peptidase 4