Characterization of muscarinic receptors mediating release of epithelial derived relaxant factor (EpDRF) in guinea-pig isolated trachea

Abstract

Muscarinic receptors mediating the release of epithelial derived relaxant factor (EpDRF) have been studied by using both contractions of the guinea-pig tracheal strip (with epithelium intact or denuded) or a coaxial bioassay assembly (rat anococcygeus-recipient; guinea-pig trachea-donor tissue). Indomethacin (1 microM/1) and physostigmine (0.1 microM/1) were both present throughout the study. In the tracheal strip studies, the potencies and maximal effects of all agonists studied (acetylcholine, arecoline, bethanechol, carbachol, (+)cis-dioxolane, ethoxyethyltrimethylammonium, L-660,863, (+/-)methacholine and OXA-22) were not affected or were only slightly (but significantly) reduced by removal of the epithelium. The -log KB for the muscarinic antagonists, atropine, pirenzepine, methoctramine and 4-DAMP (4-diphenyl-acetoxy-N-methylpiperidine) were also not affected and the -log KB values were consistent with M3 muscarinic receptor function. However, the -log KB value of para-fluoro-hexahydro-siladifendol (p-F-HHSiD) was significantly (P less than 0.05) increased upon epithelial denudation (epithelium intact, 7.1; epithelium removed, 7.6). The coaxial bioassay assembly provided more convincing evidence for release of EpDRF in that all muscarinic agonists studied caused relaxations of a precontracted anococcygeus tissue. These relaxations were observed only in the presence of a tracheal tube possessing an intact epithelium. The rank order of potencies for agonists at receptors mediating EpDRF dependent relaxation were similar to those estimated at receptors causing contraction. These data suggested that a substantial receptor reserve was associated with the receptors mediating both EpDRF release and contraction.(ABSTRACT TRUNCATED AT 250 WORDS)

Characterization of muscarinic receptors that mediate contraction of guinea‐pig isolated trachea to choline esters: effect of removing epithelium

“…It appears from these results, traction of guinea-pig trachea in the prese epithelium in response to acetic and car] esters and oxotremorine is mediated via m B values for tors. This is consistent with other findings (Eglen et al, 1991). pKB The augmentation of contraction of airway smooth muscle methoKtramine preparations to various agonists upon removal of the epi-30 mam thelium has suggested that it is stimulated release of a nonprostanoid EpDRF (s) that depresses muscle tone (Barnes et 5.7 ± 0.10 al., 1985; Flavahan et al, 1985).…”

“…The effect of remov-5.5 + 0.05 ing the epithelium on contraction to ACh may be mimicked , 1986). Also, indomethacin can impair the augmentation of contraction to acetic choline esters in this preparation 5.4± 0.06 (Eglen et al, 1991). In contrast, several studies have demonstrated that augmentation of contraction of guinea-pig tra-5.5 ± 0.06 chea to ACh and MCh upon removal of the epithelium is not 5+4 0.06 impaired by indomethacin (e.g.…”

Modulation of Adenosine-Induced Responses in the Guinea-Pig Trachea During Long-Term Caffeine Treatment: Possible Role of Epithelium

“…Experiments were also carried out in a coaxial bioassay system with a slight modification of the methods described by Fernandes et al (10), Eglen et al (11), and Hay et al (12). This bioassay involved an epithelium-intact or denuded guinea-pig tracheal tube (donor tissue) and an epithelium-denuded tracheal strip (sensor strip).…”

Characterization of postjunctional muscarinic receptors mediating contraction in rat anococcygeus muscle

“…As far as effects to exogenous cholinergic agents are concerned, the muscle responds to both muscarinic and nicotinic agonists. Muscarinic receptors located postjunctionally subserve contraction (Gillespie 1972;Oriowo 1983;Eglen et al 1991;Rand and Li 1993) and are also present on both noradrenergic and nitrergic nerve terminals where they subserve inhibition of transmission (Rajani and Gulati 1988;Li and Rand 1989). Activation of nicotinic receptors, which are present on noradrenergic and nitrergic nerve terminals, evokes release of the respective transmitters (Rand andLi 1992, 1993).…”

“…; Li and Rand 1989) and the postjunctional receptors mediating contraction (M 2 , M 3 ? ; Li and Rand 1989;Oriowo 1983;Eglen et al 1991) in RAM may be of different subtypes. However, further work appeared to be required to clarify this issue unequivocally.…”