Premium
Peripheral and central NK1 receptors in emesis control in Suncus murinus
Author(s) -
Rudd John A,
Cheng Frankie HM.,
Moreaux Benoit
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1093.30
Subject(s) - suncus , extravasation , nicotine , receptor , chemistry , pharmacology , tachykinin receptor , antagonist , endocrinology , in vivo , receptor antagonist , agonist , medicine , nk1 receptor antagonist , cisplatin , substance p , biology , immunology , neuropeptide , chemotherapy , biochemistry , microbiology and biotechnology
Brain penetrant tachykinin NK 1 receptor antagonists are known to reduce cisplatin‐induced emesis in ferrets. In the present studies, we investigate the role of central versus peripheral NK 1 receptors in the mechanism of emesis in S. murinus . R116301 was selected as a reference brain penetrant NK 1 receptor antagonist, and R115614 was used as a peripherally restricted antagonist; both have similar affinity for S. murinus NK 1 receptors (PA 2 ~8) and in vivo potency to reduce substance P‐induced plasma extravasation (ID 50 ~2.9 μmol/kg). Drugs or vehicle were administered s.c, or i.c.v. 30 min prior to nicotine (30.7 μmol/kg, s.c.), copper sulphate.5H 2 O (480.6 μmol/kg, i.g.), or cisplatin (100 μmol/kg, i.p). Peripheral Studies R116301 (23–53 mmol/kg, s.c) attenuated nicotine‐ and cisplatin‐induced emesis by 76 and 52 %, respectively (P<0.05). R115614 (30–70 mmol/kg, s.c) reduced copper sulphate‐ and cisplatin‐induced emesis by 75 and 50 %, respectively (P<0.05). Central Studies R116301 (10–100 nmol, i.c.v.) antagonised nicotine‐induced emesis 89 % (P<0.05), while R115614 (100–500 nmol, i.c.v.) was incative (P>;0.05). In conclusion, centrally located tachykinin NK 1 receptors play an important role in the emetic reflex but peripherally located NK 1 receptors may also be involved in some causes of emesis.