TY - JOUR
T1 - Ketamine inhibits agonist-induced cAMP accumulation increase in human airway smooth muscle cells
AU - Hill, Gary E.
AU - Anderson, Jodi L.
AU - Whitten, Charles W.
PY - 1999
Y1 - 1999
N2 - Purpose: Cyclic 3',5' adenosine monophosphate (cAMP) is a second messenger of the beta adrenergic receptor (BAR). Ketamine causes an increase in the intracellular accumulation of cAMP in several non-human tissue preparations. A 'species effect' may explain the differing results of ketamine on βAR mediated responses, thus reports of a ketamine-induced increase in cAMP in other species may not be applicable to humans. Methods: The effect of ketamine (10-3, 10-4, or 10-5 M) pretreatment (60 and 120 min) on isoproterenol [ISO, a beta adrenergic receptor (AR) agonist] or forskolin [FSK, an activator of adenylylcyclase (AC)]-induced intracellular accumulation of cAMP in a human airway smooth muscle (tracheal) cell line (HASM) was evaluated. In an in vitro HASM culture, cells with or without pretreatment were labeled with [3H]adenine to produce [3H]ATP, and following stimulation with ISO or FSK to convert the [3H]ATP to [3H]cAMP, the intracellular accumulation of [3H]cAMP was measured by sequential chromatography over Dowex and alumina columns. Results: Pretreatment of the HASM cells with ketamine (10-3 and 10-4 M) caused a reduction (P < 0.05, when compared to untreated cells) in ISO-induced cAMP accumulation, but did not effect cAMP accumulation following FSK stimulation. This effect of ketamine was greater at 120 min of pretreatment than at 60 min (10-3 M ketamine only)(P < 0.05). No effect was found at either time period following pretreatment of the HASM cells with ketamine 10-5M. Conclusions: These results demonstrate that pretreatment of the HASM cells with ketamine reduces ISO-induced cAMP accumulation. Since only ISO-induced cAMP was effected by ketamine, these data suggest that ketamine inhibits production of CAMP proximal to AC in the cAMP production pathway. These results also demonstrate that a mechanism other than that involving the βAR and intracellular cAMP accumulation is responsible for the ketamine induced bronchodilation in humans.
AB - Purpose: Cyclic 3',5' adenosine monophosphate (cAMP) is a second messenger of the beta adrenergic receptor (BAR). Ketamine causes an increase in the intracellular accumulation of cAMP in several non-human tissue preparations. A 'species effect' may explain the differing results of ketamine on βAR mediated responses, thus reports of a ketamine-induced increase in cAMP in other species may not be applicable to humans. Methods: The effect of ketamine (10-3, 10-4, or 10-5 M) pretreatment (60 and 120 min) on isoproterenol [ISO, a beta adrenergic receptor (AR) agonist] or forskolin [FSK, an activator of adenylylcyclase (AC)]-induced intracellular accumulation of cAMP in a human airway smooth muscle (tracheal) cell line (HASM) was evaluated. In an in vitro HASM culture, cells with or without pretreatment were labeled with [3H]adenine to produce [3H]ATP, and following stimulation with ISO or FSK to convert the [3H]ATP to [3H]cAMP, the intracellular accumulation of [3H]cAMP was measured by sequential chromatography over Dowex and alumina columns. Results: Pretreatment of the HASM cells with ketamine (10-3 and 10-4 M) caused a reduction (P < 0.05, when compared to untreated cells) in ISO-induced cAMP accumulation, but did not effect cAMP accumulation following FSK stimulation. This effect of ketamine was greater at 120 min of pretreatment than at 60 min (10-3 M ketamine only)(P < 0.05). No effect was found at either time period following pretreatment of the HASM cells with ketamine 10-5M. Conclusions: These results demonstrate that pretreatment of the HASM cells with ketamine reduces ISO-induced cAMP accumulation. Since only ISO-induced cAMP was effected by ketamine, these data suggest that ketamine inhibits production of CAMP proximal to AC in the cAMP production pathway. These results also demonstrate that a mechanism other than that involving the βAR and intracellular cAMP accumulation is responsible for the ketamine induced bronchodilation in humans.
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U2 - 10.1007/BF03015528
DO - 10.1007/BF03015528
M3 - Article
C2 - 10608213
AN - SCOPUS:0033398820
SN - 0832-610X
VL - 46
SP - 1172
EP - 1177
JO - Canadian Journal of Anesthesia
JF - Canadian Journal of Anesthesia
IS - 12
ER -