Beta-funaltrexamine discriminates between two subtypes of mu2-opioid receptors in electrically stimulated longitudinal muscle of guinea pig ileum.
1. Morphine inhibited twitch responses of the longitudinal muscle of the guinea pig to electrical stimulation. A concentration-response curve of morphine was partly inhibited by a 60-min pretreatment of ileal strip with 10(-10) M of beta-funaltrexamine (beta-FNA). However, the 60-min pretreatment with a higher concentration (10(-9) M) of beta-FNA had no further significant inhibitory effect on the curve of morphine, suggesting that beta-FNA discriminated between two subtypes of mu2 receptors, beta-FNA-sensitive and -resistant receptors. 2. The mu2 receptors in synaptosomal fraction were selectively labeled by [3H]naloxone, and the labeled receptors were competitively inhibited by morphine. The competitive-inhibition curve of morphine showed the presence of high- and low-affinity sites. Beta-FNA eliminated the high-affinity site only when endogenous GTP or GTPgamma-S was present. 3. Beta-FNA discriminated between two subtypes of mu2 receptors.
Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi, Chiba, Japan.
I
I
Takayanagi
A
A
Okayasu
K
K
Koike
T
T
Suzuki
Y
Y
Kizawa
D000109:Acetylcholine / Q000502:physiology; D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D004558:Electric Stimulation; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
D009292:Narcotic Antagonists; D017450:Receptors, Opioid, mu; D009270:Naloxone; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013779:Tetrodotoxin; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine; D000109:Acetylcholine