Investigation of relaxant effects of propofol on sheep sphincter of Oddi.
OBJECTIVE
Intravenous anesthetics are often used for conscious sedation in endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincter of Oddi (SO) manometry. This study was designed to investigate the effects of propofol on sheep SO.


METHODS
SO rings were mounted in a tissue bath and tested for changes in isometric tension in response to propofol (10(-8)-10(-4)M) in the presence or absence of L-NAME (3 x 10(-5)M), a non-specific inhibitor of nitric oxide (NO) synthase; indomethacin (10(-5)M), an inhibitor of cyclooxygenase; glibenclamide (10(-5)M), an inhibitor of ATP-sensitive potassium channels; tetraethylammonium (3 x 10(-4)M), inhibitors of calcium-activated potassium channels; 4-aminopyridine (10(-3)M), a voltage-dependent potassium channel blocker. Furthermore, we investigated the Ca(2+) antagonist feature of propofol in precontracted SO rings by CaCl(2).


RESULTS
Carbachol (10(-9)-10(-5)M) induced concentration-dependent contraction responses in the SO rings. Propofol (10(-8)-10(-4)M) produced concentration-dependent relaxation on isolated SO rings precontracted by carbachol (10(-6)M). Preincubation of SO rings by L-NAME (3 x 10(-5)M), indomethacin (10(-5)M), glibenclamide (10(-5)M), and 4-aminopyridine (10(-3)M) did not produce a significant alteration on propofol-induced relaxation responses (p > 0.05), while preincubation by tetraethylammonium (3 x 10(-4)M) significantly decreased the propofol-induced relaxation responses (p < 0.05). Propofol (10(-8)-10(-4)M) induced concentration-dependently relaxations in precontracted isolated SO rings by CaCl(2).


CONCLUSIONS
The results suggest that propofol induced concentration-dependent relaxations in precontracted isolated SO rings. These relaxations are independent from NO, cyclooxygenase metabolites, and opened ATP-sensitive and voltage-dependent potassium channels. Opened Ca(2+)-sensitive K(+) channels and inhibited L-type Ca(2+) channels existing in smooth muscle by propofol can contribute to these relaxations. Propofol can be beneficial as alternative drugs for obtaining selective relaxation during SO manometry after controlled clinical studies.
Bagcivan
Ihsan
I
Department of Pharmacology, Cumhuriyet University School of Medicine, Sivas, Turkey. ibagcivan@cumhuriyet.edu.tr
Gursoy
Sinan
S
Yildirim
M Kemal
MK
Kaya Temiz
Tijen
T
Yildirim
Sahin
S
Yilmaz
Abdulkerim
A
Turan
Mustafa
M
D015761:4-Aminopyridine / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005905:Glyburide / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*; D012756:Sheep; D009803:Sphincter of Oddi / Q000187:drug effects* / Q000503:physiopathology; D019789:Tetraethylammonium / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D004338:Drug Combinations; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin; D015742:Propofol