neurokinin-a and capsazepine

Aim Determine changes in the expressions of the ion channel-TRPV1-and neuropeptides-NKA, NKB, calcitonin gene-related peptide (CGRP), and SP-in 14-, 21-, and 42-day-old rats after inhaling 1.5% and 2.6% sevoflurane.. A small in-house inhalation anesthesia chamber was designed to allow 14-, 21-, and 42-day-old rats inhale 1.5% and 2.6% sevoflurane, and rats in the control group inhaled carrier gas(1 L/min air +1 L/min O. After inhalation of 1.5% sevoflurane, the expression of TRPV1 in the lung tissues of 14- and 21-day-old rats was significantly increased compared with that in the control group, which was antagonized by capsazepine pretreatment. Moreover, inhalation of 1.5% sevoflurane markedly increased the expressions of NKA, NKB, CGRP, and SP in the trachea of 21-day-old rats and of NKB, CGRP, and SP in the trachea of 14-day-old rats. The expressions of these molecules were antagonized by capsazepine pretreatment. Conversely, inhalation of 2.6% sevoflurane decreased the expressions of NKA and NKB in the trachea of 42-day-old rats.. Sevoflurane did not upregulate the expression of TRPV1 in the airways of late-developing rats. This anesthetic may have a two-way effect on airways, resulting in considerable effects in pediatric clinical anesthesia management.

Topics: Administration, Inhalation; Age Factors; Anesthetics, Inhalation; Animals; Blood Gas Analysis; Body Weight; Calcitonin Gene-Related Peptide; Capsaicin; Dose-Response Relationship, Drug; Neurokinin A; Neurokinin B; Rats; Rats, Sprague-Dawley; Respiration; Sevoflurane; Substance P; Trachea; TRPV Cation Channels

1. We have investigated the effects of ruthenium red and capsazepine on a C-fibre-smooth muscle preparation (the rabbit isolated iris sphincter muscle). 2. Like capsaicin, ruthenium red and capsazepine were found to produce contractions in a concentration-dependent manner. C-fibre activation was held to be responsible since the contractions could be inhibited by tachykinin receptor blockade. 3. Both ruthenium red and capsazepine inhibited capsaicin-induced contractions concentration-dependently; the pIC50 values were 5.1 and 4.9, respectively. The contractions induced by bradykinin, which, like capsaicin, acts by releasing tachykinins from C-fibres, were also inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.1 and 4.6, respectively. 4. Electrically evoked, tachykinin-mediated contractions were inhibited by ruthenium red and capsazepine in a concentration-dependent manner; the pIC50 values were 4.3 and 4.5, respectively. 5. The contractile response to neurokinin A (NKA) was inhibited by capsazepine (and by capsaicin), but not by ruthenium red, in a concentration-dependent manner; the pIC50 value was 4.3. 6. The results suggest that, besides their ability to antagonize capsaicin, ruthenium red and capsazepine possess a weak capsaicin-like effect. Conceivably, capsazepine interacts with binding sites for capsaicin, acting as a partial agonist/antagonist, while ruthenium red interacts with capsaicin-operated cation channels. The inhibition of electrically evoked- or bradykinin-induced responses by capsazepine and ruthenium red suggests that capsaicin/capsazepine binding sites and capsaicin-operated cation channels play a role in the process of transmitter release in response not only to capsaicin but also to other C-fibre stimuli. In addition, capsazepine (and capsaicin) may affect smooth muscle non-specifically since the response to NKA was also inhibited by this drug. The fact that ruthenium red did not affect the response to NKA provides further evidence that ruthenium red acts in a mode different from that ofcapsazepine.

Topics: Animals; Bradykinin; Capsaicin; Drug Interactions; Electric Stimulation; Female; Iris; Male; Muscle Contraction; Muscle, Smooth; Nerve Fibers; Neurokinin A; Neuromuscular Junction; Rabbits; Ruthenium Red

1. The ability of capsazepine, a recently developed capsaicin receptor antagonist, to prevent the effects of capsaicin on the rat isolated urinary bladder (contraction) and vas deferens (inhibition of electrically-evoked twitches) was compared to that of ruthenium red, a dye which behaves as a functional antagonist of capsaicin. 2. In the rat bladder, capsazepine (3-30 microM) produced a concentration-dependent rightward shift of the curve to capsaicin without any significant depression of the maximal response to the agonist. By contrast, ruthenium red (10-30 microM) produced a non-competitive type of antagonism, characterized by marked depression of the maximal response attainable. Similar findings were obtained in the rat isolated vas deferens in which capsazepine (10 microM) produced a rightward shift of the curve to capsaicin while ruthenium red (3 microM) depressed the maximal response to the agonist. 3. At the concentrations used to block the effect of capsaicin, neither capsazepine nor ruthenium red affected the contractile response of the rat urinary bladder produced by either neurokinin A or electrical field stimulation or the twitch inhibition produced by rat alpha-calcitonin gene-related peptide (alpha CGRP) in the vas deferens. 4. These findings provide additional evidence that both capsazepine and ruthenium red are valuable tools for exploration of the function of capsaicin-sensitive primary afferent neurones. The antagonism of the action of capsaicin by capsazepine is entirely consistent with the proposed interaction of this substance with a vanilloid receptor located on primary afferents, while the action of ruthenium red apparently involves a more complex, non-competitive antagonism.

Topics: Animals; Calcitonin Gene-Related Peptide; Capsaicin; Electric Stimulation; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Neurokinin A; Rats; Rats, Wistar; Ruthenium Red; Urinary Bladder; Vas Deferens

We have examined the effects of capsazepine, a selective capsaicin antagonist, and SR 48968, a selective NK2 receptor antagonist, on citric acid inhalation-induced bronchoconstriction in guinea-pigs. Simultaneous inhalation of capsazepine (10 microM) significantly inhibited (by 85%) the bronchoconstriction induced by inhaled citric acid (0.4 M) but not that induced by histamine (2 mM). In capsaicin-pretreated (50 mg/kg s.c. 3 weeks earlier) guinea-pigs, citric acid failed to cause any bronchoconstriction, while the effect of histamine was uninfluenced. Furthermore, citric acid inhalation-induced bronchoconstriction was also markedly inhibited (by 65%) after pretreatment with SR 48968 (0.3 mg/kg i.v.). SR 48968 blocked the bronchoconstriction but not the hypotension evoked by neurokinin A. Therefore, these results suggest that inhalation of a low-pH solution such as citric acid can stimulate sensory neurons through a mechanism similar to that for capsaicin with regard to sensitivity to capsazepine. Tachykinins such as neurokinin A are then locally released from the terminals of sensory nerves and cause bronchoconstriction, mainly by NK2 receptor mechanisms.

Topics: Administration, Inhalation; Analysis of Variance; Animals; Benzamides; Bronchoconstriction; Capsaicin; Citrates; Citric Acid; Female; Guinea Pigs; Histamine; Hydrogen-Ion Concentration; Male; Neurokinin A; Neurons, Afferent; Piperidines

Low pH is a well known sensory irritant in pathological conditions such as inflammation. The mechanisms underlying this low pH effect were therefore studied in the guinea pig. Acid exposure caused marked nasal irritation via a specific subset of sensory nerves sensitive to capsaicin. Furthermore, acid caused bronchoconstriction via release of neuropeptides from capsaicin sensitive afferents. Interestingly, capsazepine, a recently developed competitive capsaicin receptor antagonist, selectively inhibited these responses to low pH. Ruthenium red, which blocks the cation channel associated with the capsaicin receptor, had effects similar to those of capsazepine. Therefore, acid irritation of the airway mucosa may involve capsaicin-receptor mechanisms and capsazepine represents a novel protective agent.

Topics: Animals; Calcitonin Gene-Related Peptide; Capsaicin; Citrates; Citric Acid; Electric Stimulation; Guinea Pigs; Hydrogen-Ion Concentration; In Vitro Techniques; Lung; Neurokinin A; Neurons, Afferent; Nicotine; Receptors, Drug; Respiratory Physiological Phenomena; Respiratory System; Ruthenium Red; Tidal Volume; Vagus Nerve

Topics: Animals; Benzamides; Bronchoconstriction; Capsaicin; Citrates; Citric Acid; Electric Stimulation; Female; Guinea Pigs; Male; Neurokinin A; Neurons, Afferent; Piperidines; Receptors, Neurokinin-2; Receptors, Neurotransmitter