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

Abstract

A B S T R A C T 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 ug/kg for ME, 5 ,g/kg for LE, and 150 Ag/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 X 10-/ug/kg for ME, 1 ,g/kg for LE, and 150 ,ug/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 ag/kg, antagonized the response to the enkephalins while 10 jig/kg antagonized the response to MS. Higher doses of the specific-receptor agonist SKF 10047 and K-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

Colonic capacitance and transit in man: modulation by luminal contents and drugs.

“…Because of this, volumes in the right colon only during the period between 31 minutes (when the right colon was filled) and 90 minutes could be used for comparison among treatments. The median volume of the scans between 31 and 90 minutes was first computed in each subject. The effects of perfusion group and pharmacologic agent were assessed comparing pairs of groups using the two-sample t test.…”

Motor Activity of the Distal Ileum and Ileocecal Sphincter and Its Relation to the Region’s Function

“…Various prostaglan dins suppress ICS activity while the prosta glandin antagonist, indomethacin, evokes rhythmic spontaneous contractions, thus suggesting that arachidonic acid derivatives could play a role in regulating ICS tone [52]. Recent evidence suggests that feline ICS smooth muscle may possess a delta-type opiate receptor, opiate agonists inducing tonic and phasic contractions [53],…”

Vagal influence on the motility of the feline jejunum.

“…Interestingly, substance P of myenteric origin mediates NANC excitation of the longitudinal as well as the circular muscle layer of the small intestine in vitro (see Furness & Costa, 1987, for references). Naloxone-sensitive contractions in response to vagal stimulation were also demonstrated in the feline pylorus (Edin et al 1980) and ileocolonic sphincter (Ouyang et al 1982). In further support of the existence of enteric opioidergic pathways, there is abundant histochemical evidence for the presence of opioid peptide-containing Muscle excitation is primarily a result of a diminished discharge of presumably tonically active, inhibitory myenteric neurons (IMN).…”

“…Interestingly, substance P of myenteric origin mediates NANC excitation of the longitudinal as well as the circular muscle layer of the small intestine in vitro (see Furness & Costa, 1987, for references). Naloxone-sensitive contractions in response to vagal stimulation were also demonstrated in the feline pylorus (Edin et al 1980) and ileocolonic sphincter (Ouyang et al 1982 neurons in several parts of the gastrointestinal tract, including the small intestine (see Furness, LlewellynSmith, Bornstein & Costa, 1988, for references). In previous reports (Delbro & Gustafsson, 1989;Gustafsson & Delbro, 1990) we demonstrated a nonnicotinic component of the ganglionic transmission mechanism for the vagally induced opioidergic contractions.…”

“…When taken together with our previous observations that vagally induced NANC contractions could be mimicked by morphine (Gustafsson & Delbro, 1993a), an involvement of /s-opioid receptors seems likely, although d-receptors cannot be ruled out (cf. Ouyang, Clain, Snape & Cohen, 1982; for opioid receptor nomenclature, see Paterson, Robson & Kosterlitz, 1983). In some animals, a residual response was observed also after the highest dose, which could indicate the release of another NANC transmitter leading to excitation.…”