Intramural distribution of Met5-enkephalin-Arg6-Gly7-Leu8 in sphincter regions of the human gut

Ferri, Gian-Luca; Morreale, Rosalba A.; Soimero, L; Biliotti, G; Dockray, Graham J.

doi:10.1016/0304-3940(87)90314-4

Cited by 16 publications

(10 citation statements)

References 15 publications

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“…This region has been shown to contain a very high density of opioid-containing neurones in several species (Edin et al, 1980;Ferri et al, 1987;Allescher et al, 1988). We found that exogenous opioids reduced the amplitude of excitatory and inhibitory junction potentials.…”

Section: Discussionsupporting

confidence: 56%

“…Both excitatory and inhibitory junction potentials can be 17" Macmillan Press Ltd, 1993 elicited in the circular muscle of the canine pylorus (Vogalis & Sanders, 1990), and a high density of enkephalinergic nerve fibres exists in the muscularis externa of the dog (Allescher et al, 1988), as well as in man (Ferri et al, 1987) and cat (Edin et al, 1980). Opioids may have a physiological role in pyloric function since opioid agonists have been shown to delay gastric emptying (Sullivan et al, 1981).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of neural responses in the canine pyloric sphincter by opioids

Bayguinov

Sanders

1993

British J Pharmacology

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1 Regulation of excitatory and inhibitory junction potentials (ej.ps and ij.ps) by opioid peptides was studied in isolated muscle strips from the pyloric sphincter of the dog.2 Methionine enkephalin (MetEnk; 1010 to 10-6 M) and enkephalin (DADLE; 10-" to 10-' M), a 6-specific opioid agonist, inhibited ij.ps and ej.ps recorded from cells in the myenteric and submucosal regions of the circular muscle layer. These compounds had no effect on resting potential or slow wave activity suggesting that the effects on junction potentials were not due to direct effects on smooth muscle cells. 3 MetEnk and DADLE caused similar effects on junction potentials in preparations in which the myenteric plexus was removed, suggesting that opioids inhibit pre-junctional effects on nerve fibres within the muscularis externa. 4 Inhibition of junction potentials by MetEnk and DADLE was blocked by approximately the same extent by naloxone (106 M) and ICI 174,864 (106M), a 6-specific antagonist. 5 MetEnk and DADLE blocked a portion of the ij.p. that was sensitive to arginine analogues; after treatment with N0-nitro-L-arginine methyl ester (L-NAME, 10-4 M), MetEnk and DADLE had no further effect on i.j.ps. These data suggest that opioids regulate nitric oxide-dependent neurotransmission.6 Naloxone (10-6 M) alone had no effect on ij.ps elicited by short trains of electrical field stimuli. 7 Ij.p. amplitude was reduced after a period of conditioning stimulation (2 min, 30 Hz, 30 V). Naloxone blocked the post-stimulation inhibition. Repetitive stimulation at high frequencies (30 Hz) resulted in sustained hyperpolarization. Naloxone increased the amplitude of the hyperpolarization responses elicited by high frequency stimulation. 8 These results show that ej.ps and ij.ps in the canine pylorus are inhibited by opioids. A portion of the inhibitory effects appears to be mediated via 6 receptors. 9 Although pyloric muscles are richly innervated by nerves containing opioid peptides, brief trains of stimuli do not appear to release concentrations of opioids that are effective in regulating junction potentials. Higher frequency stimulation (or longer durations of stimulation) appear to be necessary to release concentrations of opioids that are effective in modulating the amplitude of junction potentials.

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Section: Discussionsupporting

confidence: 56%

Section: Introductionmentioning

confidence: 99%

Regulation of neural responses in the canine pyloric sphincter by opioids

Bayguinov

Sanders

1993

British J Pharmacology

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“…Species specific patterns, however, may occur, as very low VIP concentrations were shown in the cat anus.2 In man, it is worth noting that the pro-enkephalin Aderived peptide Met5-enkephalin-arg6-gly7-leu8, too, was little represented beyond the human sigmoid colon. 22 The presence of VIP and NPY in considerably high concentrations in the muscle layer of the human anal canal may suggest a role for such peptides in the effector control of the smooth anal sphincter. The recto-anal reflex, which inhibits the high intrinsic tone of the internal anal sphincter via a neural nonadrenergic, non-cholinergic mechamism6 has been mentioned.…”

Section: Discussionmentioning

confidence: 99%

“…*the antiscrum measurcs fully wholc mniammaliian homhcsin (gastrinreleasing peptide 1-27) and the decapeptidc of mammailiain bomhcsin (gastrin-reicasing pcptilc [18][19][20][21][22][23][24][25][26][27]; tnot cross-rcacting with PYY (<()1)/1%); tnot cross-rcacting with NPY (<()-()1I%).…”

Section: Methodsmentioning

confidence: 99%

Intramural distribution of regulatory peptides in the sigmoid-recto-anal region of the human gut.

Ferri

Adrian

Allen

et al. 1988

Gut

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SUMMARY The distribution of regulatory peptides was studied in the separated mucosa, submucosa and muscularis externa taken at 10 sampling sites encompassing the whole human sigmoid colon (five sites), rectum (two sites), and anal canal (three sites). Consistently high concentrations of VIP were measured in the muscle layer at most sites (proximal sigmoid: 286 (16) (SE). Conversely, substance P concentrations showed an obvious decline in the recto-anal muscle (mid sigmoid: 19 (2 0) pmol/g, distal rectum: 7 1 (1 3), upper anal canal: 1-6 (0 6)). Somatostatin was mainly present in the sigmoid mucosa and submucosa (37 (9 3) and 15 (3-5) pmol/g, respectively) and showed low, but consistent concentrations in the muscle (mid sigmoid: 2-2 (0 7) pmol/g, upper anal canal: 1 5 (0 8)). Starting in the distal sigmoid colon, a distinct peak of tissue NPY was revealed, which was most striking in the muscle (of mid sigmoid: 16 (3-9) pmol/g, upper rectum: 47 (7-8), anal sphincter: 58 (14)). Peptide YY was confined to the mucosa and showed an earlier peak (upper sigmoid: 709 (186) pmol/g, mid-distal sigmoid: 1965 (484)). A clear differential distribution of regulatory peptides was thus shown in the region studied. A possible role is suggested for NPY and VIP containing nerves in the effector control of the human internal anal sphincter.The whole region of the human gut composed of the sigmoid colon, rectum and anal canal can probably be considered as a complex regulatory area, devoted to the final processing and expulsion of bowel contents, culminating in defecation.' In fact, although distinct sphincteric structures are conspicuously absent at this level, the rectosigmoid junction itself has been proposed to act as a regulatory zone.' Below the rectum, a well defined smooth sphincter-that is, the internal anal sphincter, is found at the termination of the alimentary canal. ' Within this complex region, intrinsic nerves appear to play a crucial role. This is clearly the case for the inhibitory control of the internal anal sphincter, exerted by the rectoanal reflex and largely mediated

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