Comparison of effect of morphine‐like analgesics on transmurally stimulated guinea‐pig ileum

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. 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. Opiate‐induced contractions in the mouse colon were abolished by tetrodotoxin and after incubation with indomethacin. 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.

Section: Discussionmentioning

confidence: 99%

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

Fontaine¹,

Reuse²

1985

“…Only 10% of Type 2 and no Type 3 cells were affected. The concentrations of narcotics used were comparable to those required to inhibit the output of acetylcholine from the myenteric plexus (Paton, 1957;Cox & Weinstock, 1966;Fennessy, Heimans & Rand, 1969;Waterfield & Kosterlitz, 1974) or to inhibit the nerve-mediated contractile response of the longitudinal muscle (Paton & Zar, 1968;Cowie, 1968;Kosterlitz, Lord & Watt, 1973). The hyperpolarization is considered to have been mediated by opiate receptors in view of the findings that (a) the effective concentrations of agonists are low, (b) the effect is reversed by even lower concentrations of antagonists, and (c) only the (-)-isomer of optical enantiomers is effective.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Action of Narcotic Analgesics in the Guinea‐pig Ileum

North

Tonini

1977

126

Intracellular recordings were made from neurones in the myenteric plexus of the guinea‐pig ileum. Single myenteric ganglia were maintained in vitro and drugs were applied by adding them to the perfusing solution. Narcotic analgesics hyperpolarized the membrane of a proportion of neurones in the myenteric plexus. The membrane hyperpolarization was sometimes associated with a decrease in input resistance. These effects reduced the excitability of myenteric neurones. The effects of narcotics occurred at low concentrations (10 nM to 1 μM), were stereospecific and were reversed by naloxone. It is proposed that the morphine‐sensitive neurones may be the cholinergic efferents to the muscle layers. By hyperpolarizing these neurones, morphine may prevent their excitation by electric field stimulation. This may explain why narcotic analgesics reduce the output of acetylcholine and the contractile response of this preparation when it is excited by field stimulation.

“…In both tissues, the effects of morphine can be antagonized by naloxone or nalorphine (Cox & Weinstock, 1966; Matthews et al, 1973). Guinea-pig ileum has also been shown to exhibit tolerance to the effects of morphine on repeated administration, a property characteristic of morphine's effects on the central nervous system (Paton, 1957;Fennessy, Heimans & Rand, 1969). This tissue has therefore been considered a good experimental model for studying both acute and chronic effects of morphine (Paton, 1957).…”

Section: Introductionmentioning

confidence: 99%

The Role of Supersensitivity to Acetylcholine in the Production of Tolerance to Morphine in Stimulated Guinea‐pig Ileum

Shoham

Weinstock

1974

Morphine caused a dose‐dependent reduction in both the height of contraction and acetylcholine release from coaxially stimulated strips of guinea‐pig ileum. Exposure of the tissue to morphine for 90 min produced acute tolerance to the effect of subsequent doses of morphine on contraction height. There was no change in the ability of morphine to suppress acetylcholine release. The responses of morphine‐tolerant ileum to exogenous acetylcholine were enhanced 3 to 10‐fold. If the ileum did not show tolerance to morphine it did not become more sensitive to acetylcholine. The results presented suggest that tolerance to morphine could result from a form of disuse supersensitivity.