Pharmacology of colonic muscle.

Bennett, A. B.

doi:10.1136/gut.16.4.307

Cited by 35 publications

(14 citation statements)

References 43 publications

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“…Despite this, studies using human tissue in vitro have failed to demonstrate any evidence of such a spasmogenic effect of morphine (Bennett, 1975;Burleigh, 1983;Burleigh et al, 1984). This apparent lack of effect may be due to several factors: (a) morphine may not act directly on colonic smooth muscle cells, (b) the unpredictable and changing spontaneous motility of human taenia muscle strips (Bucknell & Whitney, 1966) or a complex response to electrical field stimulation ofintrinsic nerves (Stockley & Bennett, 1974) may obscure an effect ofmorphine on responses to stimulation ofintrinsic cholinergic nerves, (c) all human tissue has been obtained from major bowel resections and the opioid drugs administered before or during the operation may prevent responses to subsequent exposure of the tissue to morphine, (d) there is evidence that the gastrointestinal effects of morphine may partly result from actions on the central nervous system (Parolaro et al, 1977;Stewart et al, 1978;Burleigh et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

Morphine attenuates cholinergic nerve activity in human isolated colonic muscle

Burleigh

Trout

1986

British J Pharmacology

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The action of morphine on cholinergic nerves in human sigmoid taenia coli muscle strips (taenia) was investigated using a radiolabelling technique. Basal release of tritiated material from taenia was increased by electrical field stimulation (EFS). This increase was tetrodotoxin (3.14 μM)‐sensitive and calcium‐dependent. Analysis of basal and stimulated release of tritiated material indicated that evoked release (i.e. stimulated minus basal) is almost entirely due to an increase in [3H]‐acetylcholine ([3H]‐ACh) output. Evoked release of [3H]‐ACh was dependent on the current strength and could be greatly reduced by exposing taenia to hemicholinium (34.8, 87.0 μM) before and during incubation with [3H]‐choline (4 μCi ml−1, 15 Ci mmol−1). Spontaneous activity, muscle tone and the motor response of taenia to EFS were unaffected by morphine. Evoked, but not basal, release of tritiated material was inhibited by morphine (1.32‐13.20 μM) in a concentration‐dependent manner. The inhibition of release was frequency‐dependent and naloxone (0.28 μM)‐sensitive. The possible relationship between the effects of morphine on cholinergic nerves in taenia muscle and its actions in vivo are discussed.

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Section: Introductionmentioning

confidence: 99%

Morphine attenuates cholinergic nerve activity in human isolated colonic muscle

Burleigh

Trout

1986

British J Pharmacology

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“…Consistent with the findings of Hecker and co-workers (22,53), hemin alone produced a statistically significant increase above buffer (p ϭ 0.012), but the same heme concentration of human liver microsomes produced 15-fold more HHT. Other heme proteins, namely cytochrome b 5 , catalase, and hemoglobin did not convert PGH 2 to HHT beyond what was observed with an equivalent concentration of hemin alone (Fig. 4).…”

Section: Conversion Of Pgh 2 To Hht By Human Liver Microsomes-mentioning

confidence: 74%

“…We are investigating the possibility that COX-2 expression leads to increased DNA damage and mutation. The likely mediator of DNA damage is malondialdehyde (MDA), a product of the breakdown of PGH 2 (Fig. 1).…”

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confidence: 99%

Xenobiotic-metabolizing Cytochromes P450 Convert Prostaglandin Endoperoxide to Hydroxyheptadecatrienoic Acid and the Mutagen, Malondialdehyde

Plastaras¹,

Guengerich²,

Nebert³

et al. 2000

Journal of Biological Chemistry

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“…How ever, the system becomes less efficient and the spontaneous activity develops and in creases progressively. The role of a sympa thetic inhibitory system in the colon of var ious species has been discussed by Stockley and Bennett [1974] and Bennett [1975], Moreover, based on the analysis of the re sponses of the rat-isolated terminal colon to opiates, Gilland and Pollock [ 1980] suggested that the rat colon 'receives in addition to a motor cholinergic and perhaps an indirect inhibitory adrenergic innervation, a nonadrenergic, non-cholinergic inhibitory inner vation'. Such a complex situation might ex plain why atropine, methysergide.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of Peptides on the Rat Colon

Couture¹,

Mizrahi²,

Caranikas³

et al. 1982

Pharmacology

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Stimulatory or inhibitory effects of a number of peptides were measured on the longitudinal strip of the rat-isolated colon. Substance P, neurotensin, bombesin, enkephalins, dynorphin, angiotensin, somatostatin, eledoisin and physalemin-induced contractions of the isolated colon or increased the spontaneous activity, while the vasoactive intestinal peptide caused the tissue to relax. Several other peptides (e.g. thyroliberin, oxytocin, glucagon, insulin) were inactive. Bradykinin was a weak stimulant through the activation of B₂ receptors. Development of B₁ receptors occurred on incubation in vitro and was prevented by cycloheximide. Prolonged incubation of the rat colon strip in vitro resulted in a progressive increase of spontaneous activity and a parallel sensitization of the tissue to the actions of stimulants (e.g. substance P, carbamylcholine, angiotensin II). Significant increase of the spontaneous activity was induced by propranolol, phentolamine or phenoxybenzamine; moreover, tissues taken from reserpinized animals showed intensive spontaneous activity from the beginning of the in vitro incubation. Antihistaminics, indomethacin and baclofen were inactive, while variable effects (rapidly reversible contractions, increase in spontaneous activity) were observed in some tissues with atropine and methysergide. Spontaneous activity and the sensitivity of the colon to peptides and nonpeptide stimulants were reduced in the presence of bradykinin (BK), des-Arg⁹-BK and high concentrations (>10^–5M) of phenoxybenzamine, naloxone and verapamil. It is concluded that despite its high sensitivity to some peptides, and particularly to C-terminal fragment sequences of substance P, the rat-isolated colon appears to be a complex preparation for precise pharmacological studies on peptides because: (a) the sensitivity of the longitudinal colon strip to various stimulants increases progressively during in vitro incubation; (b) stimulants and inhibitors act not only on the smooth muscle fibers but also on the three functionally distinct sections of the intrinsic innervation, in such a way that every agent can have indirect effects, and (c) anti-adrenergic, antichoUnergic and other inhibitory drugs show intrinsic activity, therefore care must be taken when such agents are used in studies directed to demonstrate the specificity of receptors for peptides or other agonists in the rat colon.

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Pharmacology of colonic muscle.

Cited by 35 publications

References 43 publications

Morphine attenuates cholinergic nerve activity in human isolated colonic muscle

Morphine attenuates cholinergic nerve activity in human isolated colonic muscle

Xenobiotic-metabolizing Cytochromes P450 Convert Prostaglandin Endoperoxide to Hydroxyheptadecatrienoic Acid and the Mutagen, Malondialdehyde

Acute Effects of Peptides on the Rat Colon

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