CCK-4-induced calcium mobilization in T cells is enhanced in panic disorder.
We investigated the effects of brain cholecystokinin (CCK) receptors on the intracellular calcium concentration and protein kinase C in human T cells. CCK-4 produced a transient increase in calcium in the absence of extracellular calcium. CCK-B agonists stimulated calcium mobilization in a dose-dependent manner in T cells. CCK-B antagonists suppressed CCK-4-induced calcium mobilization more potently than CCK-A antagonist. The recovery of desensitization of the CCK-4-induced response was delayed by phosphoserine/phosphothreonine phosphatase inhibitor, calyculin A. The responsiveness to CCK-4 was also reduced by phorbol 12,13-dibutyrate (PDBu), and this effect of PDBu was abolished completely by preincubation with staurosporine. CCK-4-induced calcium mobilization was too small to attribute the desensitization to the protein kinase C transduction pathway. T cells from patients with untreated panic disorder exhibited significantly higher cholecystokinin-4-induced calcium mobilization than those from healthy controls or patients with treated panic disorder. These results suggest that cholecystokinin-B receptor function in T cells of patients with panic disorder is enhanced. Cholecystokinin-4-induced calcium mobilization in T cells may be state dependent and useful as a biological marker of panic disorder.
Akiyoshi
J
J
Department of Neuropsychiatry, Oita Medical University, Hasama-Machi, Japan.
Moriyama
T
T
Isogawa
K
K
Miyamoto
M
M
Sasaki
I
I
Kuga
K
K
Yamamoto
H
H
Yamada
K
K
Fujii
I
I
D000328:Adult; D000525:Alprazolam / Q000494:pharmacology; D015415:Biomarkers; D002118:Calcium / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000494:pharmacology; D016584:Panic Disorder / Q000276:immunology / Q000378:metabolism*; D010418:Pentagastrin / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000378:metabolism; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013758:Tetragastrin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000494:pharmacology*
C090019:8-sulfocholecystokinin octapeptide; D015415:Biomarkers; D018697:Nootropic Agents; D011949:Receptors, Cholecystokinin; D013758:Tetragastrin; D010418:Pentagastrin; D012844:Sincalide; D002118:Calcium; D000525:Alprazolam