Fentanyl attenuates porcine coronary arterial contraction through M3-muscarinic antagonism.
The "antimuscarinic effect" of fentanyl and its dependence on subtypes of receptors were characterized in isolated porcine coronary arteries. Left anterior descending coronary arteries were dissected from the hearts of 60 adult pigs obtained at a slaughterhouse and prepared for isometric tension studies. The effects of fentanyl on the cumulative concentration-response curve for acetylcholine were obtained in the presence and absence of muscarinic blockade by atropine. Fentanyl shifted the concentration-response curve to the right in a concentration-dependent fashion. Atropine shifted the concentration-response curve to the right, and no further shift was caused by fentanyl. To investigate the dependence on muscarinic receptor subtypes, the effect of fentanyl on acetylcholine-induced contraction was examined in the presence of specific M1-, M2-, and M3-muscarinic antagonists. The pA2 values for fentanyl decreased significantly in the presence of atropine (a nonspecific antagonist) and also in the presence of p-F-HHSiD (an M3-antagonist). In contrast, no significant change of pA2 value for fentanyl was observed in the presence of both pirenzepine (an M1-antagonist) and methoctramine (an M2-antagonist). We conclude that fentanyl has an antimuscarinic effect, and that this antagonism occurs in a competitive manner. Furthermore, the significant decrease of the pA2 value for fentanyl in the presence of M3-, but not in the presence of M1 + M2-antagonists, suggests that the attenuation of cholinergic contraction of porcine coronary arteries by fentanyl is mediated through the M3-muscarinic receptor subtype.
Yamanoue
T
T
Division of Anesthesiology, Cleveland Clinic Foundation, OH 44195-5286.
Brum
J M
JM
Estafanous
F G
FG
Khairallah
P A
PA
Ferrario
C M
CM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003864:Depression, Chemical; D005260:Female; D005283:Fentanyl / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects* / Q000502:physiology; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D010880:Piperidines; D011976:Receptors, Muscarinic; C058297:4-fluorohexahydrosiladifenidol; D010890:Pirenzepine; D001285:Atropine; D000109:Acetylcholine; D005283:Fentanyl