Airway smooth muscle relaxation induced by 5-HT(2A) receptors: role of Na(+)/K(+)-ATPase pump and Ca(2+)-activated K(+) channels.
Life Sci
; 83(11-12): 438-46, 2008 Sep 12.
Article
in En
| MEDLINE
| ID: mdl-18708073
ABSTRACT
AIMS:
Although 5-hydroxytryptamine (5-HT) contracts airway smooth muscle in many mammalian species, in guinea pig and human airways 5-HT causes a contraction followed by relaxation. This study explored potential mechanisms involved in the relaxation induced by 5-HT. MAINMETHODS:
Using organ baths, patch clamp, and intracellular Ca(2+) measurement techniques, the effect of 5-HT on guinea pig airway smooth muscle was studied. KEYFINDINGS:
A wide range of 5-HT concentrations caused a biphasic response of tracheal rings. Response to 32 microM 5-HT was notably reduced by either tropisetron or methiothepin, and almost abolished by their combination. Incubation with 10 nM ketanserin significantly prevented the relaxing phase. Likewise, incubation with 100 nM charybdotoxin or 320 nM iberiotoxin and at less extent with 10 microM ouabain caused a significant reduction of the relaxing phase induced by 5-HT. Propranolol, L-NAME and 5-HT(1A), 5-HT(1B)/5-HT(1D) and 5-HT(2B) receptors antagonist did not modify this relaxation. Tracheas from sensitized animals displayed reduced relaxation as compared with controls. In tracheas precontracted with histamine, a concentration response curve to 5-HT (32, 100 and 320 microM) induced relaxation and this effect was abolished by charybdotoxin, iberiotoxin or ketanserin. In single myocytes, 5-HT in the presence of 3 mM 4-AP notably increased the K(+) currents (I(K(Ca))), and they were completely abolished by charybdotoxin, iberiotoxin or ketanserin.SIGNIFICANCE:
During the relaxation induced by 5-HT two major mechanisms seem to be involved stimulation of the Na(+)/K(+)-ATPase pump, and increasing activity of the high-conductance Ca(2+)-activated K(+) channels, probably via 5-HT(2A) receptors.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Respiratory System
/
Serotonin
/
Sodium-Potassium-Exchanging ATPase
/
Potassium Channels, Calcium-Activated
/
Serotonin 5-HT2 Receptor Agonists
/
Serotonin 5-HT2 Receptor Antagonists
/
Muscle, Smooth
Limits:
Animals
Language:
En
Journal:
Life Sci
Year:
2008
Document type:
Article
Affiliation country:
Mexico