Field stimulation-induced responses of circular smooth muscle from guinea-pig stomach

Characterisation of the receptor mechanisms involved
  • Brenda Costall
  • Robert J. Naylor
  • Connie C. W. Tan


Field stimulation of circular smooth muscle of guinea-pig stomach from the regions of the cardia and fundus caused contraction responses at low stimulation frequencies (0.25–1 Hz) with relaxation at higher frequencies (1–10 Hz), whilst tissues of the body and antrum responded with contraction throughout the frequency range. Atropine (10−9–10−8 M) antagonised the contraction responses of all tissues, with relaxation developing at higher concentrations (except for antral tissue). In contrast, metoclopramide (10−8–10−6 M) caused modest (cardia, fundus) or marked (body, antrum) enhancement of contractions to field stimulation, whilst domperidone (10−8–10−7 M), haloperidol (10−8–10−6 M), prazosin, propranolol and methysergide (10−8–10−6 M) failed to modify the contraction responses. However, whilst yohimbine and guanethidine failed to modify the contractions of the cardia, fundus and body tissues, those of the antral preparations were antagonised by nanomolar concentrations of yohimbine and by guanethidine (10−6–5×10−5 M). To optimise the relaxation responses for study, atropine was included in the physiological solution. Relaxation to field stimulation of preparations from the body and cardia, but not the fundus, was antagonised by reserpine pretreatment (5 mg/kg i.p., 24h), addition of guanethidine (10−5–10−4 M), phentolamine, prazosin or propranolol (10−7–10−6 M) (the effects of prazosin and propranolol being additive). Higher concentrations of haloperidol and domperidone antagonised the relaxation responses of the body preparations only. Metoclopramide, yohimbine and methysergide (10−8–10−6 M) were ineffective. Thus, it is concluded that the contractile effects of the 4 stomach areas to field stimulation reflects a major cholinergic involvement, with an additional α2-adrenoceptor contractile component in antral tissue. Relaxation responses of cardia and body tissue involve α2- and β-adrenoceptors plus a further, unidentified, non-adrenergic component; the latter represents the total relaxation response of the fundic preparation.

Key words

Guinea-Pig Stomach musculature Field stimulation Cholinergic contraction Sympathetic relaxation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson JD, May MD, Watson JK (1977) Potentiation by metoclopramide of responses to cholinergic nerve stimulation in the isolated gastric fundus preparation of the rat. J Pharm Pharmacol 29:53PGoogle Scholar
  2. Bennett MR, Burnstock G, Holman ME (1966) Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli. J Physiol 182:541–558Google Scholar
  3. Burks TF (1981) Actions of drugs on gastrointestinal activity. In: Johnson LE (ed) Physiology of the gastrointestinal tract. Raven Press, New York, pp 495–516Google Scholar
  4. Burnstock G (1972) Purinergic nerves. Pharmacol Rev 24:509–581Google Scholar
  5. Bury RW, Mashford ML (1976) The effects of metoclopramide in modifying the response of the isolated guinea-pig ileum to various agonists. J Pharmacol Exp Ther 197:641–646Google Scholar
  6. Costall B, Naylor RJ, Sahyoun HA (1981) Catecholamines have a dual action on stomach strips: the relaxation component is selectively inhibited by domperidone. Br J Pharmacol 72:558P-559PGoogle Scholar
  7. Fontaine J, Reuse J (1972) Stimulation transmurale de l'ileon isole de cobaye: action du metoclopramide et du sulpiride. Arch Int Pharmacodyn Ther 197:396–398Google Scholar
  8. Hay AM (1977) Pharmacological analysis of the effects of metoclopramide on the guinea pig isolated stomach. Gastroenterology 72:864–869Google Scholar
  9. Hay AM, Man WK (1979) Effect of metoclopramide on guinea pig stomach. Critical dependence on intrinsic stores of acetylcholine. Gastroenterology 76:492–496Google Scholar
  10. Kilbinger H, Kruel R, Pfeuffer-Friedrich I, Wessler I (1982) The effects of metoclopramide on acetylcholine release and on smooth muscle response in the isolated guinea-pig ileum. Naunyn-Schmiedeberg's Arch Pharmacol 319:231–238Google Scholar
  11. Roman C (1982) Nervous control of the stomach. In: Bertaccini G (ed) Handbook of experimental pharmacology, vol 59/1 Springer, Berlin Heidelberg New York, pp 246–278Google Scholar
  12. Sahyoun HA, Costall B, Naylor RJ (1982a) On the ability of domperidone to selectively inhibit catecholamine-induced relaxation of circular smooth muscle of guinea-pig stomach. J Pharm Pharmacol 34:27–33Google Scholar
  13. Sahyoun HA, Costall B, Naylor RJ (1982b) Benzamide action at α1-adrenoceptor modifies catecholamine-induced contraction and relaxation of circular smooth muscle from guinea-pig stomach. Naunyn-Schmiedeberg's Arch Pharmacol 319:8–11Google Scholar
  14. Schuurkes JAJ, Van Nueten JM (1981) Effects of dopamine and its antagonists domperidone cannot be explained by an effect on α2-adrenergic receptors. Arch Int Pharmacodyn Ther 250:324–327Google Scholar
  15. Schuurkes JAJ, Van Nueten JM (1982) Dose dependent stimulation of antroduodenal coordination by domperidone via specific dopamine receptors. Arch Int Pharmacodyn Ther 256:311–314Google Scholar
  16. Van Nueten JM, Ennis C, Helsen L, Laduron PM, Janssen PAJ (1978) Inhibition of dopamine receptors in the stomach: an explanation of the gastrokinetic properties of domperidone. Life Sci 23:453–458Google Scholar

Copyright information

© Springer-Verlag 1983

Authors and Affiliations

  • Brenda Costall
    • 1
  • Robert J. Naylor
    • 1
  • Connie C. W. Tan
    • 1
  1. 1.Postgraduate School of Studies in PharmacologyUniversity of BradfordBradfordUK

Personalised recommendations