L-type calcium channel blockers enhance 5-HTP-induced antinociception in mice.
OBJECTIVE
To investigate the involvement of L-type Ca(2+) channels in antinociceptive action induced by the 5-HT precursor, 5-hydroxytryptophan (5-HTP).


METHODS
Female Kunming mice were treated with either 5-HTP (20-80 mg/kg, ip) alone, or the combination of 5-HTP and fluoxetine (2-8 mg/kg, ip), pargyline (15-60 mg/kg, ip), nimodipine (2.5-10 mg/kg, ip), nifedipine (2.5-10 mg/kg, ip), verapamil (2.5-10 mg/kg, ip), CaCl(2) (5-20 mmol/L, icv), or EGTA (0.5-3 mmol/L, icv) prior to the hot-plate test (55 degree, hind-paw licking latency). In addition, locomotor activity in mice treated with 5-HTP alone was measured using an ambulometer with five activity boxes.


RESULTS
Ip injection of 5-HTP alone had no influence on the spontaneous locomotor activity, whereas dose-dependently increased the latency to licking hind-paw in the hot-plate test in mice. The inhibitory effects of 5-HTP on nociceptive response were significantly enhanced by fluoxetine in the mouse hot-plate test. At a sub-effective dose, pargyline could cause a leftward shift in the dose-response curve of 5-HTP-induced antinociception. Co-administration with 5-HTP and nimodipine, nifedipine, or verapamil obviously potentiated the antinociceptive effects elicited by 5-HTP. Interestingly, 5-HTP-induced antinociception was antagonized by CaCl(2) and enhanced by EGTA injected icv in the mouse hot-plate test.


CONCLUSIONS
These findings suggest that systemic administration of 5-HTP may yield the antinociceptive effects, which are related to Ca(2+) influx from extracellular fluid through L-type Ca(2+) channels.
Liang
Jian-hui
JH
Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing 100083, China. liangjh@hotmail.com
Li
Jun-xu
JX
Wang
Xu-hua
XH
Chen
Bi
B
Lu
Ying
Y
Zhang
Pan
P
Han
Rong
R
Ye
Xiang-feng
XF
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects*; D002122:Calcium Chloride / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D007276:Injections, Intraventricular; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D010147:Pain Measurement; D010293:Pargyline / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D006916:5-Hydroxytryptophan; D000700:Analgesics; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D002122:Calcium Chloride; D002614:Chelating Agents; D004533:Egtazic Acid; D005473:Fluoxetine; D009543:Nifedipine; D009553:Nimodipine; D010293:Pargyline; D017367:Selective Serotonin Reuptake Inhibitors; D014700:Verapamil