RT Journal Article
SR Electronic
T1 Characterization of Neuromedin U Effects in Canine Smooth Muscle
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 987
OP 992
DO 10.1124/jpet.301.3.987
VO 301
IS 3
A1 Timothy D. Westfall
A1 Gerald P. McCafferty
A1 Mark Pullen
A1 Susan Gruver
A1 Anthony C. Sulpizio
A1 V. Nambi Aiyar
A1 Jyoti Disa
A1 Lisa C. Contino
A1 Ishrat J. Mannan
A1 J. Paul Hieble
YR 2002
UL http://jpet.aspetjournals.org/content/301/3/987.abstract
AB Two endogenous receptors for the potent smooth muscle-stimulating peptide neuromedin U (NmU) have recently been identified and cloned. Pharmacological, binding, and expression studies were conducted in an attempt to determine the receptor(s) involved in the smooth muscle-stimulating effects of NmU. The NmU peptides caused a concentration-dependent contraction of canine isolated urinary bladder. NmU did not have this same effect in the urinary bladder from rat, guinea pig, rabbit, mouse, or ferret. Although NmU had no effect on canine uterus it did cause contraction of canine stomach, ileum, and colon. As well as causing contraction of canine bladder in vitro, NmU administered systemically resulted in a significant increase in urinary bladder pressure in vivo. High-affinity binding sites for NmU were identified in canine bladder. The four NmU peptides porcine NmU-8, rat NmU-23, human NmU-25, and porcine NmU-25 displaced125I-NmU-25 binding with similarKi values (0.08–0.24 nM). A different binding profile was revealed in human embryonic kidney-293 cells transiently expressed with the canine NmU-2 receptor where porcine NmU-8 (Ki = 147.06 nM) was much less potent than the other NmU peptides. Using TaqMan, expression of NmU-1 was detected in human urinary bladder, small intestine, colon, and uterus. Expression of NmU-2 was much lower or absent in these human tissues and undetectable in canine bladder and stomach. The results of this study reveal significant species differences in the activity of NmU. The contractile activity in human and canine smooth muscle seems to be mediated by the recently cloned NmU-1 receptor. The American Society for Pharmacology and Experimental Therapeutics