An immunohistochemical and pharmacological study of tachykinins in the rat and guinea-pig prostate glands.
This study investigated the presence and effects of tachykinin peptides within the rat and guinea-pig prostate glands. Immunohistochemical studies demonstrated the presence of substance P and neurokinin A immunoreactive nerve fibres, sparsely distributed throughout the prostatic fibromuscular stroma in both species. In organ bath experiments, nerve terminals within rat and guinea-pig prostatic tissues were electrically field stimulated (60 V, 0.5 ms, 10 Hz, 20 pulses every 50 s). In rat preparations, the exogenous application of substance P, neurokinin A and the tachykinin NK3 receptor agonist senktide (1 nM-1 microM) had no effect on contractile responses. In contrast, substance P and neurokinin A (1 nM-3 microM) concentration-dependently enhanced electrically-evoked contractile responses in the guinea-pig prostate. Senktide was without effect. The potentiation of electrical field stimulation-induced contractions by substance P and neurokinin A in the guinea-pig prostate was competitively antagonized by ((S)1-[2-[3-(3,4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl) piperidin-3-yl]ethyl]-4-phenyl-1-azonia-bicyclo[2.2.2]octane , chloride) (SR 140333) at 10 nM, a tachykinin NK1 receptor antagonist. The tachykinin NK2 receptor antagonist (S)-N-methyl-N[4-(4-acetylamino-4-phenylpiperidino)-2-(3,4-dichloropheny l)butyl]benzamide (SR 48968) was without effect at 10 nM, suggesting that neuromodulation of electrically-evoked contractions in the guinea-pig prostate occurs through activation of a tachykinin NK1 receptor subtype.
Buljubasich
S
S
Department of Pharmacology, Monash University, Clayton, Victoria, Australia.
Lau
W A
WA
Pennefather
J N
JN
Ventura
S
S
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001549:Benzamides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D015288:Neurokinin A / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011467:Prostate / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D015320:Tachykinins / Q000494:pharmacology*
D001549:Benzamides; D010446:Peptide Fragments; D010880:Piperidines; D011812:Quinuclidines; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C054724:senktide; C085215:SR 140333; D013373:Substance P; C073839:SR 48968; D001285:Atropine; D015288:Neurokinin A