Contractor responses of the isolated colon of the mouse to morphine and some opioid peptides

Abstract

1 Morphine (1 times 10⁻⁸-1 times 10⁻⁴M), fentanyl (1 times 10⁻⁹− 1 times 10⁻⁵M) and alfentanyl (1 times 10⁻¹⁰ − 1 times 10⁻⁵M) as well as methionine enkephalin [Met⁵]enkephalin (1 times 10⁻¹¹ − 1 times 10⁻⁸M), [D-Ala², Met⁵]enkephalin (1 times 10⁻¹² − 1 times 10⁻⁸M) and dynorphin A(1 − 13) (1 times 10⁻⁹ − 1 times 10⁻⁶M) caused a contractor response of the longitudinal musculature of the terminal colon of the mouse. 2 These effects were competitively antagonized by naloxone. The pA₂ values obtained for naloxone antagonism of morphine and opioid peptides and the high sensitivity of the preparation to enkephalins suggest the presence of δ-opiate receptors in this preparation but μ-and κ-receptors may also be present. 3 Opiate-induced contractions in the mouse colon were abolished by tetrodotoxin and after incubation with indomethacin. 4 It is concluded that the excitatory actions of the opiates in the mouse colon are mediated via opiate receptors located on nerves which do not release acetylcholine, noradrenaline or 5-hydroxytryptamine. The opiates may produce their action by removing an inhibitory neural influence (the nature of which remains to be elucidated) allowing a prostaglandin-mediated effect to predominate, thereby increasing muscle tone.