Neurokinin receptors in the rat lower urinary tract.
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.
Maggi
C A
CA
Pharmacology Department, A. Menarini Pharmaceuticals, Florence, Italy.
Parlani
M
M
Astolfi
M
M
Santicioli
P
P
Rovero
P
P
Abelli
L
L
Somma
V
V
Giuliani
S
S
Regoli
D
D
Patacchini
R
R
D000818:Animals; D004600:Eledoisin / Q000378:metabolism; D015286:Kassinin; D008297:Male; D009842:Oligopeptides / Q000378:metabolism; D010643:Phenoxybenzamine / Q000494:pharmacology; D010803:Physalaemin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013373:Substance P / Q000031:analogs & derivatives / Q000378:metabolism; D014513:Ureter / Q000187:drug effects / Q000378:metabolism; D014521:Urethra / Q000187:drug effects / Q000378:metabolism; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism; D014551:Urinary Tract / Q000378:metabolism*
D009842:Oligopeptides; D018041:Receptors, Neurokinin-2; D017981:Receptors, Neurotransmitter; D010643:Phenoxybenzamine; D010803:Physalaemin; D013373:Substance P; D015286:Kassinin; D004600:Eledoisin; C033611:substance P, methyl ester-