Characterization of Opiate-mediated Responses of the Feline Ileum and Ileocecal Sphincter

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Abstract

Although opioid peptides have been demonstrated immunohistochemically in the feline intestine, the action of these peptides is unknown. The aims of this study were: (a) to determine the distal ileal and ileocecal sphincter (ICS) responses to morphine sulfate (MS), methionine enkephalin (ME) and leucine enkephalin (LE); (b) to determine the mechanism by which exogenous opiates mediate these responses; (c) to determine the type of receptor involved in mediating these responses and (d) to ascertain whether endogenous opiate-mediated responses may be vagally induced. The ICS responded to all three opiate agonists with tonic and phasic contractions, the latter being associated with increased spike activity. The EDmax for ICS pressure response was 1 μg/kg for ME, 5 μg/kg for LE, and 150 μg/kg for MS. The distal ileum responded with increased spike activity and phasic contractions. The EDmax for the ileal motility index response was 1.0 × 10−1 μg/kg for ME, 1 μg/kg for LE, and 150 μg/kg for MS. Thus, both sites demonstrated similar dose-response relationships, both responding to at least 100 times lower doses of enkephalins than MS. The ICS contraction preceded ileal contractions. The ileal and ICS response was not antagonized by atropine, hexamethonium, phentolamine, propranolol, cinanserin, or tetrodotoxin. Naloxone, 600 μg/kg, antagonized the response to the enkephalins while 10 μg/kg antagonized the response to MS. Higher doses of the specific-receptor agonist SKF 10047 and κ-receptor agonist ketocyclazocine were required before a contractile response was elicited. Electrical stimulation of the cervical vagus induced ICS contraction and a fall in blood pressure. The ICS contractile response but not the blood pressure response was inhibited by naloxone 1 mg/kg. These data indicate: (a) tonic and phasic ICS contraction followed by ileal contraction may be mediated through δ-type opiate receptors located in the muscle membrane and (b) opiate-mediated ICS contraction may be induced during vagal stimulation.

Authors

Ann Ouyang, Carole J. Clain, William J. Snape Jr., Sidney Cohen