ISSN:
1432-1912
Keywords:
Intestinal secretion
;
Chloride transport
;
Guinea pig colon
;
Opioid peptides
;
Opioid antagonists
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Summary The influence of four opioid antagonists on short circuit current (Isc), transepithelial potential difference (Pdo) and tissue conductance (Gt) in the guinea pig colonic mucosa was investigated in vitro under both basal and PGE1 plus theophylline-stimulated conditions. The experiments aimed at identifying the opioid receptor type(s) endogenously activated to control chloride secretion. Under blockade of sodium-dependent Isc by amiloride (100 µmol/I), net anion secretion was regarded to equal the lumen-negative shift in Isc upon addition of 1 µmol/l PGE1 plus 100 gmol/l theophylline. It was significantly elevated by 100 nmol/l of the ϰ-selective antagonist nor-binaltorphimine (nor-BNI). This augmenting effect was totally abolished in amiloride-free buffer or by omission of chloride. 1 µmol/l TTX completely prevented the effect of both PGE1 plus theophylline and nor-BNI. Both the ϰ agonist U 69593 (10 nmol/l) and the calcium channel agonist Bay K 8644 (1 µmol/l) significantly depressed net anion secretion stimulated by PGE1 plus theophylline. Nor-BNI at 10 nmol/l prevented the suppressive effect of both Bay K 8644 and U 69593. This suggests release of endogenous opioids by the calcium channel agonist Bay K 8644 and competition between the ϰ agonist U 69593 and the ϰ antagonist nor-BNI. In contrast to the ϰ antagonist nor-BNI, the µ antagonist CTOP-NH2 at 100 nmol/l significantly impaired, while the µ-selective agonist DAGO at 0.2 nmol/l augmented, net anion secretion stimulated by PGE1 plus theophylline. The effect of CTOP-NHn2 was abolished in chloride-free buffer. The δ selective antagonist ICI 174.864 (up to 1 µmol/l) and the non-selective antagonist naloxone (up to 1 µmol/l) failed to influence stimulated net anion secretion. The failure of naloxone may be due to superimposition of the contrasting effects of µ and ϰ receptor blockade by a high naloxone concentration. The antagonist effect of nor-BNI considered above was obtained at 9.6 nmol/l potassium but was no longer observed when the potassium concentration in the bathing solution was reduced to 4.8 mmol/l. It is suggested that both elevated potassium concentration and calcium channel activation by Bay K 8644 release endogenous ϰ agonists in the guinea pig colonic mucosa under the present conditions. Since CTOP-NH2 impaired stimulated net anion secretion at both of the potassium concentrations, release of endogenous µ agonists and, hence, activation of µ opioid receptors seem to take place under both conditions. In conclusion, the present work demonstrates for the first time that activation of ϰ opiod receptors by endogenous opioid peptides impair, while activation of µ opioid receptors augment, stimulated chloride secretion in this tissue.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00183012
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