Reduced inflammation in genetically hypertensive rat airways is associated with reduced tachykinin NK(1) receptor numbers.

Abstract

The airways of the genetically hypertensive rat (GH) are hyperinnervated by substance P-containing sensory nerves and exhibit reduced inflammatory responsiveness to substance P and to capsaicin. The present study measured tracheal inflammation to resiniferatoxin (1.0 microgram/kg i.v.), a capsaicin analogue, which lacks the hypotensive action of capsaicin itself, alone or after the neuronal nitric oxide synthase inhibitor 1-(2-trifluoromethylphenyl)imidazole (TRIM) (50 mg/kg i.p.). The inflammatory response to resiniferatoxin alone was 50% lower in untreated GH than in control rats, a similar strain difference to that seen previously with capsaicin. Pre-treatment with TRIM had no effect on inflammation in either strain. Binding kinetics of the tachykinin NK(1) receptor antagonist [3H](S)-1-(2-[3-(3, 4-dichlorophenyl)-1-(3-isopropoxyphenylacetyl)piperidin-3-yl]ethyl)-4- phenyl-l-azoniabicyclo[2,2,2,]octane chloride ([3H]SR140333)(0.125-16.0 nM) showed 50% reduction of B(max) in GH versus control tracheae (74+/-13 cf.165+/-26 fmol/mg protein). Our results indicate that the reduced neurogenic inflammatory responsiveness in GH rats can be attributed entirely to reduced tachykinin NK(1) receptor numbers.

• Authors: V A Campbell, P Beddy, A Foley, Y S Bakhle, C Bell
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 401 Issue 1 Pg. 109-14 (Jul 28 2000) ISSN: 0014-2999 [Print] Netherlands
• PMID: 10915843 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Diterpenes
• Piperidines
• Quinuclidines
• Receptors, Neurokinin-1
• Tritium
• SR 140333
• Substance P
• resiniferatoxin

Topics

• Animals
• Binding, Competitive (drug effects)
• Capillary Permeability (drug effects)
• Diterpenes (pharmacology)
• Hypertension (genetics, physiopathology)
• Inflammation (metabolism, physiopathology)
• Male
• Membranes (drug effects, metabolism)
• Piperidines (metabolism)
• Quinuclidines (metabolism)
• Radioligand Assay
• Rats
• Rats, Inbred Strains
• Receptors, Neurokinin-1 (drug effects, metabolism)
• Spinal Cord (drug effects, metabolism)
• Substance P (pharmacology)
• Trachea (drug effects, metabolism, physiopathology)
• Tritium