Saadet Inan
Temple University
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Publication
Featured researches published by Saadet Inan.
Pharmacology, Biochemistry and Behavior | 2006
Saadet Inan; Alan Cowan
Scratching is the behavioral manifestation of pruritus. The pruritus of cholestasis can be severe, intractable and affect the quality of life. We investigated if ethynylestradiol (EE)-induced cholestasis is associated with scratching in rats and if nalfurafine, a kappa opioid receptor agonist with antipruritic effects in human uremic pruritus, would antagonize such scratching. Chronic injection of EE (2 mg/kg, s.c., for 14 days) induced cholestasis as documented by increased serum concentrations of bile acids and caused a higher incidence of body scratching compared to vehicle, thus providing an animal model to study scratching behavior secondary to cholestasis. Pretreating the rats with nalfurafine (0.005-0.04 mg/kg, s.c.) inhibited EE-induced scratching dose-dependently with an A(50) value of 0.013 (0.009-0.021) mg/kg. Serum levels of dynorphin A and nitric oxide were decreased in rats with cholestasis compared to control animals. Our data suggest that (a) nalfurafine has the potential to relieve cholestatic pruritus and (b) both kappa opioid and nitric oxide systems are involved, at least in part, in mediating the pruritus of cholestasis.
Brain Research | 2005
Scott M. Rawls; Jennifer Marie Hewson; Saadet Inan; Alan Cowan
Despite insights into an increasingly significant role for delta opioid receptors in thermoregulation, it is unclear whether delta receptors located in the brain or periphery play the more critical role in body temperature regulation. Moreover, it is not entirely clear which delta receptor phenotype, delta1 or delta2, mediates the hypothermic actions of delta agonists. Because SNC-80 distributes into central and peripheral compartments and produces rapid hypothermia following systemic injection, the nonpeptide delta agonist is particularly useful in discriminating the site of action of delta receptor-mediated hypothermia. To determine the locus and phenotype of delta receptor which mediates SNC-80-induced hypothermia, we injected SNC-80 and phenotype selective delta antagonists to male Sprague-Dawley rats. SNC-80 (10-50 mg/kg, im) evoked hypothermia that peaked 30 min post-injection. Naltrexone (5 mg/kg, sc), an opioid antagonist, or naltrindole (5 mg/kg, sc), a delta antagonist, blocked the hypothermic response to SNC-80 (35 mg/kg, im). The hypothermia caused by SNC-80 (35 mg/kg, im) was blocked by a delta2 antagonist, naltriben (2.5 mg/kg, sc), but was not affected by BNTX (5 and 10 mg/kg, sc), a delta1 antagonist. The administration of naltriben (10 microg/rat, icv) 30 min before SNC-80 (35 mg/kg, im) prevented SNC-80-evoked hypothermia. In contrast, methylnaltrexone (5 mg/kg, sc), a peripherally restricted opioid antagonist, did not affect the hypothermia caused by SNC-80. The present data demonstrate that selective activation of brain delta2 receptors is a major mechanism of SNC-80-evoked hypothermia in rats.
Archive | 2009
Alan Cowan; Saadet Inan
Norbinaltorphimine (norBNI), the prototype kappa-opioid receptor antagonist, N-benzylnorBNI, and 5′-guanidinonaltrindole (GNTI) precipitate stereotyped scratching after subcutaneous injection behind the neck of Swiss-Webster mice. The intensity of the behavioral activation and its repetitive nature represent one of the most arresting sights in preclinical psychopharmacology. The rank order for both potency and efficacy was GNTI > norBNI > N-benzylnorBNI. Although nalfurafine, the clinically tested kappa-opioid receptor agonist, decreased the incidence of GNTI-induced compulsive scratching in a dose-related manner, it is likely that this antagonism is mediated by mechanisms additional to a possible direct interaction with kappa receptors.
Journal of Pharmacology and Experimental Therapeutics | 2018
Saadet Inan; Toby K. Eisenstein; Mia N Watson; Menahem Doura; Joseph J. Meissler; Christopher S. Tallarida; Xiaohong Chen; Ellen B. Geller; Scott M. Rawls; Alan Cowan; Martin W. Adler
Crossdesensitization between opioid and chemokine receptors and involvement of chemokines in pain modulation are well established. We investigated if coadministration of chemokine receptor antagonists (CRAs) with morphine would enhance the analgesic potency of morphine on incisional pain in rats. Animals underwent incisional surgery on the left hind paw and pain responses were evaluated using von Frey filaments at various time points postsurgery between 15 and 360 minutes and daily between 24 and 72 hours. Dose-response curves for morphine, maraviroc (a CCR5 antagonist), and AMD3100 (a CXCR4 antagonist) alone were established. While morphine significantly reduced pain in a time- and dose-dependent manner, maraviroc and AMD3100 had no effect by themselves. Coadministration of either maraviroc or AMD3100 with morphine significantly increased morphine’s analgesic effect on incisional pain, shifting the dose-response curve to the left 2.3- and 1.8-fold, respectively. Coadministration of both CRAs with morphine significantly shifted further the morphine dose-response curve to the left 3.3-fold. The effect of treatments on mRNA levels in the draining popliteal lymph node for a panel of chemokines and cytokines showed that message for many of these mediators was upregulated by the incision, and the combination of morphine with the CRAs markedly downregulated them. The data show that combining morphine with CRAs potentiates morphine’s analgesic effect on incisional pain. Thus, the same analgesic effect of morphine alone can be achieved with lower doses of morphine when combined with CRAs. Using morphine in lower doses could reduce unwanted side effects and possibly block development of tolerance and dependence.
Endocrinology | 2007
G. Cristina Brailoiu; Siok L. Dun; Eugen Brailoiu; Saadet Inan; Jun Yang; Jaw Kang Chang; Nae J. Dun
Journal of Pharmacology and Experimental Therapeutics | 2004
Yulin Wang; Kang Tang; Saadet Inan; Daniel J. Siebert; Ulrike Holzgrabe; David Y.-W. Lee; Peng Huang; Jian-Guo Li; Alan Cowan; Lee-Yuan Liu-Chen
European Journal of Pharmacology | 2004
Saadet Inan; Alan Cowan
Neuroscience | 2009
Saadet Inan; Nae J. Dun; Alan Cowan
European Journal of Pharmacology | 2009
Saadet Inan; Nae J. Dun; Alan Cowan
Peptides | 2011
Saadet Inan; Nae J. Dun; Alan Cowan