Faculty Collaboration Database

Serotonin modulated Ca++ dependent K+ channels in alloimmune effector cell lytic function. Immunopharmacol Immunotoxicol 1989;11(2-3):165-78

Date

01/01/1989

Pubmed ID

2559929

DOI

10.3109/08923978909005363

Scopus ID

2-s2.0-0024787724 (requires institutional sign-in at Scopus site)   7 Citations

Abstract

Potassium channel activity has been implicated in the lytic function of cloned murine effector T lymphocytes (5) and human NK cells (12) as well as in the initiation of the injury process in tumor cells (23). In the present studies, the effects of various K+ channel blockers on the cytolytic function of in vivo derived alloimmune lymphocytes towards P815 tumor cells were evaluated. The classical K+ channel blocker 4-aminopyridine (4-AP), the naturally occurring monoamine serotonin (5-hydroxytryptamine, 5-HT) and its agonist, quipazine, as well as the Ca++ dependent K+ channel blocker quinidine were chosen for investigation based on their known ion channel gating properties. These agents, when present in the assay medium, inhibited in a dose dependent manner the lysis of P815 tumor cells as measured by specific 51Cr release. Preincubation of effector lymphocytes with the various K+ channel blockers resulted in greater inhibition of lysis than did the preincubation of target cells. The 5-HT agonist quipazine was of particular interest in that it inhibited the lytic process with equal effectiveness when continuously present in the assay medium or when the effector cells alone were preincubated. Quinidine was used to investigate whether Ca++ dependent K+ channels were the predominant ion channel involved in the lytic process. When present during the lytic assay, quinidine was similar to quipazine in terms of their dose range at which they inhibited the lytic process. These results indicate that 5-HT sensitive Ca++ dependent K+ channels are likely to be involved in the delivery of lytic signal(s) by immune effector lymphocytes and suggests that neuroendocrine products may modulate the functional activity of in vivo derived lymphocytes.

Author List

Liepins A, LeFever A, Truitt RL

Author

Robert L. Truitt PhD Emeritus Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

4-Aminopyridine
Animals
Calcium
Cytotoxicity, Immunologic
Killer Cells, Natural
Lymphocytes
Mice
Potassium Channels
Quinidine
Quipazine
Serotonin
T-Lymphocytes, Cytotoxic
Tumor Cells, Cultured