Capsaicin treatment induces muscarinic hyperreactivity in guinea pig trachea: a warning.
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is a widely used tool for the depletion of neuropeptides from sensory C-fibres. Upon capsaicin treatment tachykinins are released, resulting in a variety of responses in the airways. We showed that after capsaicin (0.3 microM; 30 min) treatment of guinea pig tracheal smooth muscle preparations, the maximal contraction of the trachea after methacholine stimulation was strongly increased (capsaicin: 1.147 +/- 0.050 g vs. control: 0.717 +/- 0.047 g). This effect was completely nullified after pretreatment with capsazepine (2-[2-(4-chlorophenyl)ethyl-amino-thiocarbonyl]-7,8-dihydroxy-2,3, 4,5-tetrahydro-1H-2benzazepine; a vanilloid receptor antagonist) and YM38336 (a dual tachykinin NK1 and tachykinin NK2 receptor antagonist). Our results serve as a warning against using capsaicin as a putatively clean pharmacological tool to deplete the neuropeptides from pools on the C-fibres because we showed that capsaicin also strongly influences basal mechanisms in tracheal smooth muscle control.
van Hoof
H J
HJ
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Faculty of Chemistry, Vrije Universiteit, Amsterdam, Netherlands.
den Hartog
G J
GJ
Voss
H P
HP
van Bree
L
L
Bast
A
A
D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D016210:Methacholine Chloride / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D011976:Receptors, Muscarinic / Q000187:drug effects*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D018039:Receptors, Tachykinin; D016210:Methacholine Chloride; C071423:capsazepine; D002211:Capsaicin