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Inhibitory effects of tramadol on nicotinic acetylcholine receptors in adrenal chromaffin cells and in Xenopus oocytes expressing α7 receptors
Author(s) -
Shiraishi Munehiro,
Minami Kouichiro,
Uezono Yasuhito,
Yanagihara Nobuyuki,
Shigematsu Akio,
Shibuya Izumi
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704703
Subject(s) - nicotinic agonist , endocrinology , catecholamine , medicine , chromaffin cell , chemistry , tramadol , nicotine , acetylcholine receptor , acetylcholine , receptor , (+) naloxone , adrenal medulla , pharmacology , carbachol , opioid , biology , analgesic
Tramadol has been used clinically as an analgesic; however, the mechanism of its analgesic effects is still unknown. We used bovine adrenal chromaffin cells to investigate effects of tramadol on catecholamine secretion, nicotine‐induced cytosolic Ca 2+ concentration ([Ca 2+ ] i ) increases and membrane current changes. We also investigated effects of tramadol on α7 nicotinic acetylcholine receptors (AChRs) expressed in Xenopus oocytes. Tramadol concentration‐dependently suppressed carbachol‐induced catecholamine secretion to 60% and 27% of the control at the concentration of 10 and 100 μ M , respectively, whereas it had little effect on veratridine‐ or high K + ‐induced catecholamine secretion. Tramadol also suppressed nicotine‐induced ([Ca 2+ ] i ) increases in a concentration‐dependent manner. Tramadol inhibited nicotine‐induced inward currents, and the inhibition was unaffected by the opioid receptor antagonist naloxone. Tramadol inhibited nicotinic currents carried by α7 receptors expressed in Xenopus oocytes. Tramadol inhibited both α‐bungarotoxin‐sensitive and ‐insensitive nicotinic currents in bovine adrenal chromaffin cells. In conclusion, tramadol inhibits catecholamine secretion partly by inhibiting nicotinic AChR functions in a naloxone‐insensitive manner and α7 receptors are one of those inhibited by tramadol.British Journal of Pharmacology (2002) 136 , 207–216; doi: 10.1038/sj.bjp.0704703