Neurokinin receptors in the rat lower urinary tract

Abstract

The effects of neurokinins (NKs), tachykinins and some NK-related peptides (selective agonists for the NK-1, NK-2 or NK-3 receptors) have been investigated in the various sections of the rat lower urinary tract. In the isolated bladder, all peptides were substantially equipotent with the exception of senktide, an NK-3 agonist, which was distinctly less potent than the other compounds. Similar results were obtained in the isolated urethra. In these tissues, the maximal response to NK-1 agonists was distinctly less intense than that to the other peptides. In the bladder, exposure to phenoxybenzamine (30 microM for 90 min) reduced the response to NK-A but not that to substance P, KCl or field stimulation. In the isolated ureter, peptides active at both the NK-2 and the NK-3 sites [including senktide and [MePhe7]-NKB(4-10)] activated, at nanomolar concentrations a series of rhythmic contractions, whereas peptides active at the NK-1 site, were active only at micromolar concentrations. These findings provide further evidence that multiple NK receptors are present in the rat lower urinary tract. In the bladder, NK-2 and NK-1 sites mediate the direct response to NKs, in accordance with binding and autoradiographic data. In the ureter, both NK-2 and NK-3 sites may activate the direct contractile response to these substances.