Action of nicotine on guinea-pig isolated bronchial smooth muscle preparation

doi:10.1016/0306-3623(84)90013-2

General Pharmacology: The Vascular System

Volume 15, Issue 4, 1984, Pages 349-352

General Pharmacology...

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Abstract

1. In the isolated bronchial preparation of the guinea-pig, nicotine induced a contraction but not a relaxation. The contractile response of the bronchial preparation to nicotine was inhibited by hexamethonium and d-tubocurarine but not influenced by atropine and tetrodotoxin.

2. In the isolated tracheal preparation of the guinea-pig where nicotine stimulated nicotinic receptor in nervous tissues, the contractile response to nicotine as considerably accelerated by the treatment of the guinea-pig with egg-albumin, while the contractile response of the bronchial preparation to nicotine was not influenced by the same treatment.

3. These results suggest that a possible site of action of nicotine in the isolated bronchial preparation is not on the nervous cells but on the smooth muscle cells.

4. However, we could not rule out a contribution by chemical mediators released by nicotine in the contractile mechanisms in the bronchial preparation.

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Cited by (17)

Mechanism of relaxation induced by nicotine in normal and ovalbumin-sensitized guinea-pig trachea
2007, European Journal of Pharmacology
Nicotine is an irritant molecule in the cigarette that contributes airway hyper-reactivity. The aim of this study was to investigate the mechanism of these effects and effects of nicotine on the isolated trachea preparations from control and ovalbumin-sensitized guinea-pigs. Nicotine (3 × 10^− 5 to 3 × 10^− 4 M) produced concentration-dependent relaxation on isolated trachea preparations precontracted by carbachol (10^− 6 M) in both groups. We found that the relaxant effect of nicotine decreased in the presence of N(w)-nitro L-arginine methyl ester (L-NAME) (10^− 6 M), and hexamethonium (10^− 2 M) but not in the presence of α-bungarotoxin (10^− 3 M), and tetrodotoxin (3.1 × 10^− 6 M) in isolated trachea preparations in both groups. The relaxant effect of nicotine was less significant in isolated trachea preparations from ovalbumin-sensitized guinea-pigs than from control guinea-pigs (P < 0.05). The contractions elicited by carbachol (10^− 6 M) were not significantly different in the ovalbumin-sensitized group than in the control group. Nicotine (10^− 4 M) significantly increased the cGMP levels in trachea preparations compared with the control preparations.(P < 0.05). These results suggest that nicotine-induced relaxation response in normal and ovalbumin sensitized guinea-pigs trachea is at least in part mediated by nitric oxide (NO) since it was significantly reduced in the presence of L-NAME. The decreased relaxation response to nicotine in ovalbumin sensitized guinea-pigs trachea may be due to impaired production and/or liberation of NO.
Control by cholinergic mechanisms
2006, European Journal of Pharmacology
In the respiratory tract acetylcholine is neurotransmitter in ganglia and postganglionic parasympathetic nerves, but in addition is paracrine mediator released from various non-neuronal cells. Almost every cell type present in the respiratory tract expresses nicotinic and muscarinic receptors and therefore appears to be a target for acetylcholine. The present review describes the mechanisms of synthesis and release of acetylcholine from neuronal and non-neuronal cells and the differential control mechanisms. The different cholinoceptors, multiple nicotinic and muscarinic receptors and their signalling are outlined and their involvement in the modulation of the function of various target cells, smooth muscles, nerves, surface epithelial, secretory cells, fibroblasts and inflammatory cells is discussed in detail.
Hyperresponsiveness to tobacco dust extract in sensitized guinea pig trachea
2004, Pulmonary Pharmacology and Therapeutics
The role of pre-existing airway inflammation in the pathogenesis of occupational airway disease is poorly understood. Previously we studied an extract of tobacco dust (TDE) and determined that it causes concentration dependent contractions of nonsensitized guinea pig trachea (GPT). In the present study animals were sensitized using Ovalbumin (OA) and subsequently challenged with an aerosol of 2.5% OA on day 21. A control group of nonsensitized GPs were divided into rings in which the epithelium was retained (EPI+) or removed (EPI−). Concentration related contractions of sensitized and nonsensitized GPTs were elicited with TDE. Sensitized GPTs demonstrated a greater contractile response to TDE than did nonsensitized GPTs. In nonsensitized animals the EPI− GPTs demonstrated a lesser response to TDE than did the EPI+. Similar findings were demonstrated in sensitized GPTs with and without epithelium. When epithelium was removed, sensitized and nonsensitized GPTs behaved similarly. Moreover, sensitized GPTs without epithelium and nonsensitized with epithelium responded similarly. These findings suggest that presensitization with an unrelated antigen enhances the response to an occupational agent and that in sensitized animals at least part of the enhanced response is mediated by the epithelial layer.
Inhibitory effects of d-nicotine on the responses evoked by 1-isomer in trachea and bronchus isolated from guinea-pig and rabbit
1995, General Pharmacology
- 1.
  1. The effects of d-nicotine on the responses induced by 1-isomer were studied in tracheae and bronchi isolated from guinea-pigs and rabbits. In guinea-pig trachea 1-nicotine produced a biphasic response consisting of initial contraction and following relaxation. In other airway preparations 1-nicotine produced only contraction.
- 2.
  2. d-Nicotine did not produce any responses except for the case of guinea-pig trachea. d-isomer produced only relaxation and relative potency was approximately 0.44 in guinea-pig trachea.
- 3.
  3. Pretreatment with d-nicotine (30 ∼ 300 μM) reduced concentration response curves for 1-isomer in a non-competitive manner in all preparations used in this study.
- 4.
  4. 1-nicotine at the concentration of 3 μM, which did not produce any response itself, reduced the concentration response curve of 1-nicotine in guinea-pig trachea.
- 5.
  5. Inhibition by d-nicotine or 1-nicotine (3 μM) of the concentration-response curve of 1-nicotine may be due to desensitization of nicotine receptors.
Effect of ageing on response to nicotine in rabbit bronchial preparation
1991, General Pharmacology
- 1.
  1. Effect of ageing on the response to nicotine was tested in the bronchial muscle preparations from 5, 13, 100 and 125 week-old rabbits. The pD₂ value (potency) of nicotine significantly increased in the preparation from the 125 week-old rabbits. No age-related change was found in the pD₂ value of carbamylcholine or pA₂ value of atropine.
- 2.
  2. No age-related change in characteristics of nicotine receptors. Choline acetyltransferase activity, the amount of acetylcholine released by nicotine and acetylcholineesterase activity decreased in the preparations from the 125 week-old rabbits.
- 3.
  3. Decrease in the pD₂ value of nicotine in the preparation from the older rabbit is due to a decline in choline acetyltransferase activity followed by a reduction in the acetylcholine released, and not to a change in characteristics of nicotine receptors.
- 4.
  4. These results also suggest that enzymes may be influenced more easily with age than drug receptors.
Effect of ageing on nicotine-induced contraction of guinea-pig bronchial preparation
1990, General Pharmacology
- 1.
  1. Nicotine-induced contraction of bronchial preparations isolated from 3, 6, 10, 50 and 100 week old guinea-pigs were studied.
- 2.
  2. Contractile responses to nicotine were inhibited by hexamethonium and a substance P antagonist but not by atropine or tetrodotoxin, suggesting that the nicotine-contraction was mediated through a release of substance P-like material(s).
- 3.
  3. The pD₂ value (potency) of nicotine did not change with age from 3 to 10 weeks but decreased thereafter to 100 weeks, while no age-related change was found in the pD₂ vaule of substance P. The pA₂ value of hexamethonium did not change with age, suggesting that the affinity of drugs to nicotine receptors does not change with age.
- 4.
  4. These results suggest the possibility that age-related change in the pD₂ value of nicotine is due to a change in the amount of nicotine receptors but not to a change in the affinity of nicotine to its receptors.

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Action of nicotine on guinea-pig isolated bronchial smooth muscle preparation

Abstract

Jap J. Pharmac.

Eur. J. Pharmac.

Gen. Pharmac.

Jap. J. Pharmac.

Jap. J. Phrmac.

The tracheal chain I. A preparation for study of antispasmodics with particular response to bronchodilator drugs

J. Pharmac. exp. Ther.