Modulation of murine lymphocyte functions by sulfated cholecystokinin octapeptide.
The effects in vitro of the sulfated octapeptide form of cholecystokinin (CCK-8) at concentrations ranging from 10(-13) M to 10(-6) M on several functions of murine lymphocytes were studied, i.e. adherence to substrate, mobility (spontaneous and directed by chemical gradient or chemotaxis) and spontaneous and phytohemagglutinin (PHA)-mediated proliferation. Lymphocytes were obtained from peritoneal suspension as well as from axillary nodes, spleen and thymus of BALB/c mice. CCK-8, at concentrations from 10(-10) M to 10(-8) M, significantly inhibited the mobility capacity and the PHA-induced proliferation and increased the adherence and the spontaneous proliferation of lymphocytes. A dose-response relationship was observed, with a maximum effect on lymphocyte functions at 10(-10) M. In addition, CCK-8 induced a significant decrease in membrane and cytosol protein kinase C (PKC) activity in murine lymphocytes, as well as an increase of intracellular cyclic AMP levels. These results suggest that CCK-8 is a negative modulator of two important lymphocyte functions in the immune response, i.e. mobility and mitogen-induced proliferation, and that the PKC activity inhibition and cAMP increase could be the mechanisms through which CCK inhibits these lymphocyte activities.
De la Fuente
M
M
Departamento de Biología Animal II (Fisiología Animal), Facultad de Ciencias Biológicas, Universidad Complutense de Madrid, Spain.
Carrasco
M
M
Del Rio
M
M
Hernanz
A
A
D000818:Animals; D001365:Axilla; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D010835:Phytohemagglutinins / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology; D013950:Thymus Gland / Q000166:cytology; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D010835:Phytohemagglutinins; D014660:Vasoactive Intestinal Peptide; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000242:Cyclic AMP; D011493:Protein Kinase C; D012844:Sincalide