Tachykinin NK-2 receptors in child urinary bladder.

ABSTRACT

PURPOSE: Although NK-2 receptors mediate contractions to tachykinins in adult detrusor muscle, little is known about the functions of tachykinins in child urinary bladder. Here we have used highly selective agonists and antagonists to examine NK-2 receptors in child detrusor muscle. MATERIALS AND METHODS: Specimens of urinary bladder from 23 children (0 to 10 years0 were obtained at operation for vesicoureteric reflux. Strips of detrusor muscle were mounted in organ baths in Krebs solution containing phosphoramidon (10 microM.), and isometric tension was recorded. Contractile responses were elicited by tachykinins and selective agonists in the presence and absence of autonomic inhibitors and of tachykinin NK-2 receptor antagonists. RESULTS: The NK-2 receptor agonists neurokinin A (NKA), neuropeptide gamma and [Lys5, MeLeu9, Nle10]-NKA(4-10) contracted the isolated child detrusor, with pD2 values of 7.7, 7.2 and 7.3. The maximum response to NKA was greater than that to the other 2 agonists. No age-related differences were seen. Selective agonists for NK-1 receptors ([Sar9, Met(O2)11]-SP and septide) and NK-3 receptors (senktide) were ineffective contractile agents. Responses to NKA were unaffected by phentolamine (5 microM.), propranolol (3 microM.), tetrodotoxin (1 microM.) and indomethacin (1 microM.), indicating a direct action on smooth muscle. The tachykinin NK-2 receptor antagonists SR 48968 and MEN 10627 caused a concentration-dependent antagonism of responses to NKA, with apparent pKB values of 9.4 and 8.1. CONCLUSIONS: Neurokinin A appears to act directly on NK-2 receptors on detrusor muscle of infant and child urinary bladder, without involvement of neural or indirect contractile mechanisms. Potency of antagonists was similar to that seen in other tissues. However, agonist potency was significantly lower in the isolated detrusor from children, compared with our previous study in adult detrusor. This discrepancy may be related to age-related differences in NK-2 receptors or in contractile mechanisms; alternatively it may be a result of the reflux condition.