In vitro contractile effects of neurokinin receptor blockade in the human ureter.

Abstract

PURPOSE:

We identified the predominance of neurokinin-2 receptors and evaluated the inhibition of spontaneous contraction via the blockade of neurokinin-2 receptors in human ureteral segments.

MATERIALS AND METHODS:

Excess ureteral segments from human subjects undergoing donor nephrectomy or reconstructive procedures were suspended in tissue baths containing Krebs buffer. After spontaneous contractions were recorded, tissues were incubated with 1 microM. solutions of phosphoramidon and captopril (to inhibit peptide degradation) and either the neurokinin-1 receptor antagonist CP 99,994, the neurokinin-2 receptor antagonist SR 48,968, the neurokinin-3 receptor antagonist SR 142,801 or dimethyl sulfoxide (control) for 1 hour. Contraction magnitude and frequency were again recorded and compared with spontaneous levels. Concentration-response curves to the tachykinins substance P, and neurokinins A and B were determined in the presence and absence of antagonists.

RESULTS:

Neurokinin A increased contractility at lower concentrations than substance P or neurokinin B (p <0.013). Neurokinin-2 receptor blockade produced a 100-fold rightward shift of the concentration-response curves (p <0.013), while neurokinins 1 and 3 receptor blockade had no effect. SR 48,968 significantly reduced contractility during the 1-hour incubation period, causing a 97% reduction in spontaneous rates compared with a 29% reduction in control tissues. CP 99,994 and SR 142,801 had no significant effect.

CONCLUSIONS:

Neurokinin-2 is the predominant receptor subtype responsible for tachykinin induced contraction of human ureteral smooth muscle. In vitro treatment with the neurokinin-2 antagonist SR 48,968 reduces the spontaneous contraction rate by 97% in vitro. Neurokinin-2 receptor antagonists may have clinical applications for ureteral disease.

• Authors: S Y Nakada, T J Jerde, D E Bjorling, R Saban
• Journal: The Journal of urology (J Urol) Vol. 166 Issue 4 Pg. 1534-8 (Oct 2001) ISSN: 0022-5347 [Print] United States
• PMID: 11547127 (Publication Type: Journal Article)

Chemical References

• Angiotensin-Converting Enzyme Inhibitors
• Benzamides
• Glycopeptides
• Piperidines
• Receptors, Neurokinin-2
• Tachykinins
• 3-(2-methoxybenzylamino)-2-phenylpiperidine
• SR 48968
• Captopril
• Metalloendopeptidases
• SR 142801
• phosphoramidon

Topics

• Angiotensin-Converting Enzyme Inhibitors (pharmacology)
• Benzamides (pharmacology)
• Captopril (pharmacology)
• Dose-Response Relationship, Drug
• Glycopeptides (pharmacology)
• Humans
• Metalloendopeptidases (antagonists & inhibitors)
• Muscle Contraction (drug effects)
• Piperidines (pharmacology)
• Receptors, Neurokinin-2 (antagonists & inhibitors, physiology)
• Tachykinins (pharmacology)
• Ureter (physiology)