Effects of cholinergic blockade, adrenergic blockade and sympathetic denervation on gastrointestinal myoelectric activity in guinea pig

J. J. Galligan, J. B. Furness, M. Costa

    Research output: Contribution to journalArticle

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    Abstract

    Gastrointestinal myoelectric activity was recorded from conscious guinea pigs using sets of bipolar electrodes that had been surgically implanted onto the serosal surface of the gastric antrum or small intestine. The role of nerves in the control of the migrating myoelectric complex (MMC) was investigated using cholinergic and adrenergic receptor antagonists, guanethidine to block sympathetic transmission, reserpine to deplete intestinal monoamines and 6-hydroxydopamine (6-OHDA) to produce chemical sympathectomy and surgical sympathetic denervation of the stomach and small intestine. Subcutaneous infusion of hyoscine (1.0 or 3.0 mg/kg and 1.0 or 3.0 mg/kg/hr) blocked the initiation of phase 3 of the MMC. In the presence of hyoscine, intermittent electrical spiking comparable to that of phase 2 of the MMC was recorded. Hexamethonium infusion (3.0 or 10.0 mg/kg and 3.0 or 10.0 mg/kg/hr) also blocked the initiation of phase 3 and reduced the frequency of the intermittent spiking activity. Acute blockade of adrenergic receptors by simultaneous s.c. infusion of phentolamine and propranolol (1.0 mg/kg and 1.0 mg/kg/hr of each drug) did not alter the MMC, whereas infusion of guanethidine (3.75 or 7.5 mg/kg and 3.75 or 7.5 mg/kg/hr) increased the frequency of the MMC by significantly shortening the duration of phase 2. Sympathetic denervation of the stomach and small intestine did not block the MMC but decreased the cycle frequency by significantly prolonging the duration of phase 2. Chemical sympathectomy using 6-OHDA treatment (3 x 250 mg/kg s.c.) also did not abolishe the MMC but decreased the frequency by increasing the duration of phase 2. Reserpine treatment (2.5 mg/kg s.c.) decreased the frequency of the MMC to a greater extent than that produced by 6-OHDA treatment. Histochemical and immunohistochemical evaluation of tissues taken from denervated, 6-OHDA- and reserpine-treated animals confirmed that surgical denervation removed sensory and adrenergic nerves to the stomach and small intestine, whereas chemical sympathectomy affected only adrenergic neurons. Reserpine treatment depleted norepinephrine from extrinsic adrenergic neurons and also depleted 5-hydroxytryptamine from intrinsic intestinal neurons. In the guinea pig, antral myoelectric activity is briefly inhibited during duodenal phase 3. Gastric inhibition persisted during duodenal phase 3 in surgically denervated animals, in 6-OHDA-treated animals and in animals treated acutely with guanethidine. These results indicate that extrinsic sensory and sympathetic nerves are not required for the initiation and propagation of the MMC in the guinea pig small intestine. Sympathetic neurons and possibly intrinsic 5-hydroxytryptamine-containing neurons modify the frequency of the cycle. Phase 3 is dependent on cholinergic transmission through muscarinic and nicotinic receptors, whereas phase 2 depends on cholinergic transmission through nicotinic receptors and may also involve noncholinergic transmission or myogenic factors. Gastric inhibition associated with duodenal phase 3 does not require intact sympathetic nerves.

    Original languageEnglish
    Pages (from-to)1114-1125
    Number of pages12
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume238
    Issue number3
    Publication statusPublished - 1 Sep 1986

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