Increase of plasma corticosterone induced by loperamide in rats

Giagnoni, Gabriella; Parolaro, Daniela; Sala, Mariaelvina; Marabini, Laura; Senini, R.; Gori, E

doi:10.1016/0014-2999(82)90579-9

Cited by 5 publications

(4 citation statements)

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“…In the rat, however, Giagnoni et al [17] have found a stimulating effect of loper amide on ACTH secretion. Similar increases of ACTH secretion by morphine have been shown to be mediated by activating CRH-release and sympathetic neuronal pathways [15,16].…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, in the rat, p-opiate agonists like morphine and loperamide increase ACTH secretion by activating central mechanisms [15][16][17]. In vitro, however, Lamberts et al [18] have reported a suppressive effect of the p-opiate agonist FK 33-824 on ACTH secretion from rat ante rior pituitary lobes which was not reversed by naloxone [18], Rittmaster et al [13] have found no effect of mor phine on ACTH secretion from perifused rat anterior pi tuitary cells.…”

Section: Introductionmentioning

confidence: 99%

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Loperamide Inhibits Corticotrophic Cell Function by a Naloxone-lnsensitive Mechanism in the Rat in vitro

Auernhammer

Renner

Müller³

et al. 1993

Neuroendocrinology

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The effect of the antidiarrheal drug loperamide, a µ-opiate agonist, on ACTH secretion and biosynthesis, cAMP generation and phosphoinositide turnover was studied in rat anterior pituitary cell cultures. The cAMP-dependent protein kinase A pathway was stimulated with both corticotropin-releasing hormone (CRH; 2–5 nM) and the membrane-permeable Bu(2)cAMP (0.5–2.5 mM). The protein kinase C pathway was stimulated with 1 µM arginine vaso-pressin (AVP) and 1-10 nM phorbol 12-myristate 13-acetate (PMA). After 3.5 h, loperamide (10 µM) had no effect on basal ACTH levels but significantly suppressed CRH-induced ACTH release, in a dose-dependent manner, to 60 ± 4% of control (100%) (p < 0.0001). After 24 h, basal proopiomela-nocortin mRNA was significantly decreased to 50% of control by loperamide (p < 0.05). The suppressive effect of loperamide on CRH-induced ACTH secretion was not reversible by naloxone (0.1-1,000 µM). Morphine (0.01-10 µM) had no effect on basal and CRH-induced ACTH secretion. Loperamide did not influence basal and CRH-induced adenylate cyclase activity in anterior pituitary cell membrane preparations, but it significantly blunted Bu₍₂₎cAMP-induced ACTH secretion in cell culture from 100 ± 4 to 77 ± 4% (p < 0.05). In Ca²⁺-depleted medium (Ca²⁺ < 0.1 mM), loperamide had no suppressive effect on CRH-induced ACTH secretion. AVP-induced ACTH secretion was significantly suppressed by loperamide from 100 ± 5 to 74 ± 3% (p < 0.0001), while basal and AVP-induced inositol 1-phosphate generation and PMA-induced ACTH secretion were not affected by loperamide. In comparison with the known effects of the calmodulin-inhibitors trifluoperazine, W-7 and penfluridol, loperamide mimicked all their effects on ACTH secretion. We conclude: (1) the effects of loperamide on corticotrophic cell function in vitro are naloxone-insensitive and not mediated by µ-opiate receptors; and (2) our data provide a strong argument for loperamide working as a calmodulin inhibitor in the rat anterior pituitary in vitro.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Loperamide Inhibits Corticotrophic Cell Function by a Naloxone-lnsensitive Mechanism in the Rat in vitro

Auernhammer

Renner

Müller³

et al. 1993

Neuroendocrinology

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“…altering expression of c-Fos in the paraventricular nucleus (PVN): site of CRF neurons known to initiate ACTH secretion Cooper, 1984,1986;Coventry et al, 2001;Giagnoni et al, 1982;Houshvar et al, 2001a,b;Suemaru et al, 1986;Zhou et al, 1999). However, in other studies, loperamide and the mu-selective agonists fentanyl decreased basal levels of ACTH as well CRH-induced ACTH and cortisol in rat cultures (Auernhammer et al, 1993).…”

Section: Preclinical Studies Of Acth and Cortisol Interactions With Mmentioning

confidence: 99%

“…The mu-selective agonists loperamide (Giagnoni et al, 1982) and morphine increased ACTH and corticosterone in rats possibly via a CRF-independent mechanism; e.g. altering expression of c-Fos in the paraventricular nucleus (PVN): site of CRF neurons known to initiate ACTH secretion Cooper, 1984,1986;Coventry et al, 2001;Giagnoni et al, 1982;Houshvar et al, 2001a,b;Suemaru et al, 1986;Zhou et al, 1999).…”

Section: Preclinical Studies Of Acth and Cortisol Interactions With Mmentioning

confidence: 99%

Effects of nalbuphine on anterior pituitary and adrenal hormones and subjective responses in male cocaine abusers

Goletiani

Mendelson

Sholar

et al. 2007

Pharmacology Biochemistry and Behavior

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Nalbuphine (Nubain®) is a mixed action mu-kappa agonist used clinically for the management of pain. Nalbuphine and other mu-kappa agonists decreased cocaine self-administration in preclinical models. Cocaine stimulates the hypothalamic-pituitary-adrenal (HPA) axis, but the effects of nalbuphine on the HPA axis are unknown. Analgesic doses (5 and 10 mg/70 kg) of IV nalbuphine were administered to healthy male cocaine abusers, and plasma levels of PRL, ACTH and cortisol were measured before and at 10, 17, 19, 23, 27, 31, 35, 40, 45, 60, 75, 105, 135 min after nalbuphine administration. Subjective effects were measured on a Visual Analog Scale (VAS). Prolactin (PRL) increased significantly within 17 min (P=.04) and reached peak levels of 22.1 ± 7.1 ng/ml and 54.1 ± 11.3 at 60 min after low and high dose nalbuphine administration, respectively. VAS reports of "Sick," "Bad" and "Dizzy" were significantly higher after 10 mg/70 kg than after 5 mg/70 kg nalbuphine (P=.05−.0001), and were significantly correlated with increases in PRL (P=.05−.0003). However, sedation and emesis were observed only after a 10 mg/70 kg dose of nalbuphine. Interestingly, ACTH and cortisol levels did not change significantly after administration of either dose of nalbuphine. Taken together, these data suggest that nalbuphine had both mu-and kappa-like effects on PRL (PRL increase) but did not increase ACTH and cortisol.

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