Sigma receptor activation does not mediate fentanyl-induced attenuation of muscarinic coronary contraction.
Our overall goal was to investigate the mechanism by which fentanyl attenuates acetylcholine-induced contraction in porcine coronary artery. We tested the hypothesis that fentanyl attenuates muscarinic coronary contraction via sigma receptor activation. Left coronary artery vascular rings were isolated from porcine hearts and were suspended in organ chambers for isometric tension recording. In untreated coronary vascular rings, acetylcholine administration resulted in dose-dependent contraction. Fentanyl attenuated acetylcholine-induced contraction. The sigma ligands--(+)-pentazocine, (+)-cyclazocine, haloperidol, and 1,3-di-o-tolylguanidine--also inhibited acetylcholine-induced contraction. In contrast, the selective sigma ligand, (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine failed to have an inhibitory effect on acetylcholine-induced contraction. Moreover, metaphit (1-[1(3-isothiocyanatophenyl)cyclohexyl]piperidine), which causes irreversible acylation of sigma receptors, only inhibited acetylcholine-induced contraction when it was present in the organ chamber. We also assessed the effects of inhibiting various points in the signal transduction pathway distal to naloxone-sensitive opioid receptor activation on acetylcholine-induced contraction. Selective (glybenclamide) and nonselective (tetraethylammonium) K(+)-channel inhibition, guanosine triphosphate-binding protein inactivation (pertussis toxin), and Type 1 and Type 2 dopamine receptor inhibition all failed to alter the attenuating effect of fentanyl on acetylcholine-induced contraction. Thus, neither sigma or opioid receptor activation is a prerequisite for fentanyl-induced inhibition of muscarinic coronary contraction.
Tsuchida
H
H
Center for Anesthesiology Research, Cleveland Clinic Foundation, OH 44195, USA.
Schubert
A
A
Estafanous
F G
FG
Brum
J M
JM
Murray
P A
PA
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects*; D003496:Cyclazocine / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005283:Fentanyl / Q000008:administration & dosage / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D009116:Muscarine / Q000008:administration & dosage / Q000494:pharmacology*; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000008:administration & dosage / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011954:Receptors, Dopamine / Q000187:drug effects; D017480:Receptors, sigma / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D006146:Guanidines; D018721:Muscarinic Agonists; D009292:Narcotic Antagonists; D009294:Narcotics; D010880:Piperidines; D026902:Potassium Channel Blockers; D011954:Receptors, Dopamine; D017480:Receptors, sigma; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009116:Muscarine; C044705:metaphit; C026539:preclamol; D010622:Phencyclidine; D003496:Cyclazocine; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D000109:Acetylcholine; D010423:Pentazocine; D005283:Fentanyl