Inhibitory effect of pasireotide and octreotide on lymphocyte activation.
Somatostatin (SST) regulates the function of the central and peripheral nervous system, the endocrine and exocrine organs, as well as the vascular and immune system. These actions are mediated by five specific membrane somatostatin receptors. This study compares the effects on human lymphocytes of two long-acting somatostatin analogues that have different receptor affinity: octreotide and pasireotide. Both analogues have an antiproliferative effect on human lymphocyte proliferation, but they act at different concentration and, while octreotide enhances IL10 and inhibits gamma IFN pasireotide inhibits IL2 and gamma IFN. In both sets of experiment the different behaviour of the two analogues could be due to their different affinity to the SSTR subtypes. Finally this study suggest that the growth inhibitory action of somatostatin analogues is an apoptotic phenomenon and it can be mediated by SSTR2a, in the case of octreotide, and by SSTR3 when pasireotide is used or it can be mediated by the heterodimerization of the two receptor.
Lattuada
D
D
Department of Pharmacology, School of Medicine, University of Milan, Italy. donatella.lattuada@unimi.it
Casnici
C
C
Crotta
K
K
Mastrotto
C
C
Franco
P
P
Schmid
H A
HA
Marelli
O
O
D000328:Adult; D017209:Apoptosis / Q000502:physiology; D001667:Binding, Competitive; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000378:metabolism; D007376:Interleukin-2 / Q000037:antagonists & inhibitors; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D015282:Octreotide / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009842:Oligopeptides / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D009994:Osmolar Concentration; D017481:Receptors, Somatostatin / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives
D007376:Interleukin-2; D009842:Oligopeptides; D017481:Receptors, Somatostatin; C103631:somatostatin receptor 3; D016753:Interleukin-10; D013004:Somatostatin; D007371:Interferon-gamma; C517782:pasireotide; C093733:somatostatin receptor 2; D015282:Octreotide