1. This study was undertaken to investigate whether, after a brief exposure of guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid agonist also possessing antagonist activity at mu-opioid receptors, the addition of opioid antagonists produced withdrawal contractures. Our aim was to verify in these tissues the existence of an interaction between the mu- and kappa-opioid systems. 2. In guinea-pig ileum preparations previously exposed for 5 min to bremazocine at 5.7 x 10(-7) M and 5.7 x 10(-8) M, naloxone (5 x 10(-7) M) elicited no response whereas in tissues exposed to a lower bremazocine concentration (5.7 x 10(-9) M), naloxone (5 x 10(-7) M) and the selective kappa-opioid antagonist, nor-binaltorphimine (3.4 x 10(-8) M) both produced a strong contracture. 3. Bremazocine (5.7 x 10(-7) M) administered to guinea-pig isolated ileum, previously exposed for 5 min to morphine (10(-7) M), induced a withdrawal contracture. In contrast, lower bremazocine concentrations (1.4 and 7.1 x 10(-8) M) did not elicit a withdrawal contracture. 4. Naloxone (5 x 10(-7) M), added to the bath after a 5 min exposure of guinea-pig ileum to morphine (10(-7) M), elicited the characteristic withdrawal contracture. Bremazocine (1.4-7.1 x 10(-8) M) added 1 min before naloxone (5 x 10(-7) M) inhibited the naloxone withdrawal contracture in a dose-related way whereas naloxone 5 x 10(-8) M added 1 min before naloxone 5 x 10(-7) M, did not affect the withdrawal response. 5. In the rabbit jejunum, bremazocine (1.4-7.1 x 10-8 M) caused a decrease in amplitude in the spontaneous tissue activity. In tissues exposed to these bremazocine concentrations, naloxone(5 x 10-7 M) elicited a marked contracture. A similar contracture occurred when nor-binaltorphimine(3.4 x 10-8 M) was added in place of naloxone. These effects were dose-related to the bremazocine concentration. The specific K-agonist, U-50,488H (5 x 10-8 M), elicited the same effects as bremazocine.6. These findings show that stimulation of K-opioid receptors induces a state of dependence that is not prevented by blocking the pi-opioid system. The observation that low bremazocine concentrations inhibit the morphine-induced withdrawal contractures, indicates an interaction between the micro- and K-opioid system in guinea-pig isolated ileum, similar to that observed in the whole animal.

Acute withdrawal after bremazocine and the interaction between mu- and kappa-opioid receptors in isolated gut tissues. / Valeri, P; Morrone, Luigi Antonio; Romanelli, L; Amico, Mc. - In: BRITISH JOURNAL OF PHARMACOLOGY. - ISSN 0007-1188. - 114:6(1995), pp. 1206-1210.

Acute withdrawal after bremazocine and the interaction between mu- and kappa-opioid receptors in isolated gut tissues.

MORRONE, Luigi Antonio;
1995

Abstract

1. This study was undertaken to investigate whether, after a brief exposure of guinea-pig isolated ileum and rabbit jejunum to bremazocine, a kappa-opioid agonist also possessing antagonist activity at mu-opioid receptors, the addition of opioid antagonists produced withdrawal contractures. Our aim was to verify in these tissues the existence of an interaction between the mu- and kappa-opioid systems. 2. In guinea-pig ileum preparations previously exposed for 5 min to bremazocine at 5.7 x 10(-7) M and 5.7 x 10(-8) M, naloxone (5 x 10(-7) M) elicited no response whereas in tissues exposed to a lower bremazocine concentration (5.7 x 10(-9) M), naloxone (5 x 10(-7) M) and the selective kappa-opioid antagonist, nor-binaltorphimine (3.4 x 10(-8) M) both produced a strong contracture. 3. Bremazocine (5.7 x 10(-7) M) administered to guinea-pig isolated ileum, previously exposed for 5 min to morphine (10(-7) M), induced a withdrawal contracture. In contrast, lower bremazocine concentrations (1.4 and 7.1 x 10(-8) M) did not elicit a withdrawal contracture. 4. Naloxone (5 x 10(-7) M), added to the bath after a 5 min exposure of guinea-pig ileum to morphine (10(-7) M), elicited the characteristic withdrawal contracture. Bremazocine (1.4-7.1 x 10(-8) M) added 1 min before naloxone (5 x 10(-7) M) inhibited the naloxone withdrawal contracture in a dose-related way whereas naloxone 5 x 10(-8) M added 1 min before naloxone 5 x 10(-7) M, did not affect the withdrawal response. 5. In the rabbit jejunum, bremazocine (1.4-7.1 x 10-8 M) caused a decrease in amplitude in the spontaneous tissue activity. In tissues exposed to these bremazocine concentrations, naloxone(5 x 10-7 M) elicited a marked contracture. A similar contracture occurred when nor-binaltorphimine(3.4 x 10-8 M) was added in place of naloxone. These effects were dose-related to the bremazocine concentration. The specific K-agonist, U-50,488H (5 x 10-8 M), elicited the same effects as bremazocine.6. These findings show that stimulation of K-opioid receptors induces a state of dependence that is not prevented by blocking the pi-opioid system. The observation that low bremazocine concentrations inhibit the morphine-induced withdrawal contractures, indicates an interaction between the micro- and K-opioid system in guinea-pig isolated ileum, similar to that observed in the whole animal.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/138771
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