Morphine Modulates Contractile Responses and Neurokinin A-LI Release Elicited by Electrical Field Stimulation or Capsaicin in a Guinea Pig Bronchial-tube Preparation

Abstract

Excitatory nonadrenergic, noncholinergic (e-NANC) bronchoconstrictor responses have been shown to be mediated by the release of tachykinins from sensory nerves. We investigated whether bronchial-tube contractions evoked by electrical-field stimulation (EFS) or capsaicin coincided with the release of neurokinin A (NKA). We also studied the modulatory action of morphine and the ability of naloxone to affect these responses. We used a guinea pig bronchial-tube preparation denuded of epithelium. The method allows simultaneous measurement of smooth-muscle tension and mediator release. A significant release of NKA-LI, at 37.3% above the basal level, was detected in response to EFS. Morphine pretreatment was found to inhibit the release, and such inhibition was not prevented by naloxone. Contractile responses to EFS coincided with the NKA-LI release. Capsaicin stimulation evoked a significant release (35.4%) of NKA-LI, and this release was accompanied by contractions. Treatment with morphine decreased capsaicin-induced responses, and naloxone reversed the inhibitory effect. In conclusion, both capsaicin- and EFS-induced e-NANC responses were inhibited by morphine treatment. This indicates presynaptic inhibition of tachykinin release from sensory nerves. Furthermore, the ability of naloxone to reverse this inhibitory effect differed in capsaicin- and EFS-challenged preparations.

Effects of κ- and μ-opioid agonists on cholinergic neurotransmission and contraction in isolated bovine trachealis

“…This conclusion was further supported by the observation that, in both guinea pig and human trachealis, EFS stimulation of opioid receptors inhibits ACh release from cholinergic nerves (Patel et al, 1997(Patel et al, , 1999. But inhibition of excitatory non-cholinergic nonadrenergic nerves (eNANC) has not been excluded (Belvisi et al, 1990;Lindström and Andersson, 1995;Matran et al, 1989).…”

Nociceptin inhibits non‐adrenergic non‐cholinergic contraction in guinea‐pig airway

“…Excitatory non‐adrenergic non‐cholinergic (NANC) contractile responses have been reported in guinea‐pig airway in vitro (Grundstrom et al , 1981) secondary to the release of neuropeptides such as substance P and neurokinin A. Morphine and opioid peptides have been shown to inhibit NANC contraction in guinea‐pig airway (Frossard & Barnes, 1987; Kamikawa & Shimo, 1990), substance P release from rat trigeminal nucleus slices in vitro (Jessel & Iversen, 1977) and both capsaicin‐ and electrical‐field stimulation (EFS)‐induced NANC responses in guinea‐pig perfused bronchial tubes (Lindstrom & Andersson, 1995). In recent studies, excitatory NANC contraction of guinea‐pig renal pelvis (Giuliani & Maggi, 1996) and substance P release from rat trachea (Helyes et al , 1997) was inhibited by nociceptin.…”

Neurokinin A‐LI release after antigen challenge in guinea‐pig bronchial tubes: influence of histamine and bradykinin

“…A method used to measure the muscle tension of a tracheal or bronchial‐tube preparation has been described by our research group (Grundström et al , 1992; Lindström & Andersson, 1995). In the present study, the modified method that is suitable for the bronchial‐tube preparations (Lindström & Andersson, 1995) was used. In short, the trachea and all branches of the bronchi were ligated to create a single unbranched tube actually consisting of both bronchi.…”

“…The perfusate from the bronchial‐tube preparation was collected for 10 min immediately before stimulation to obtain basal values and after that for 10 min during stimulation. The perfusate was collected on ice and acetic acid was immediately added to a final concentration of 0.5 M. Isolute‐C18 cartridges (IST, by Sorbent AB, V. Frölunda, Sweden) were then used to purify and concentrate the samples (Lindström & Andersson, 1995; Saria et al , 1988). Briefly, cartridges were activated with a methanol solution (0.1% trifluoroacetic acid containing 0.06 M sodium chloride and 80 voL % methanol) and equilibrated with TFA solution (0.1% trifluoroacetic acid in water containing 0.06 M sodium chloride).…”

“…In the present study, we addressed the question of whether antigen challenge of airway preparations stimulates capsaicin‐sensitive sensory nerves and thereby increases outflow of tachykinins. We used sensitized guinea‐pig bronchialtube preparations (Lindström & Andersson, 1995) to determine NKA‐LI outflow and smooth muscle tension in response to both antigen and capsaicin challenge. Involvement of histamine H 1 receptors and bradykinin B 2 receptors was examined by using the histamine H 1 receptor antagonist pyrilamine and the selective bradykinin B 2 receptor antagonist icatibant (Hock et al , 1991).…”