Adenosine selectively inhibits noncholinergic transmission in guinea pig bronchi

Abstract

The neuromodulatory action of adenosine and ATP was investigated in isolated guinea pig bronchial strip chain preparations contracted with electrical field stimulation. The tissues were placed in organ baths containing physiological salt solution and stimulated at 8-Hz frequency, 0.5-ms pulse duration, and 30 V (approximately 100 mA) for 5 s. Electrical field stimulation evoked a biphasic contraction of bronchial muscle, consisting of an initial contraction followed by a sustained contraction, which was mediated by intramural cholinergic and noncholinergic nerve stimulations, respectively. Adenosine, at concentrations greater than M, caused a concentration-dependent inhibition in the height of the noncholinergically mediated contraction, accompanied by a very weak inhibition on the cholinergically mediated response. ATP (10(-5) to 3 x 10(-3) M) also produced a similar inhibitory effect on the noncholinergically mediated contraction, but the inhibitory potency was less than that of adenosine. The inhibitory response to adenosine was enhanced by the pretreatment with dipyridamole (2 x 10(-6) M) but antagonized with aminophylline (10(-5) M). Contractions of bronchial muscle evoked by exogenous acetylcholine (2 x 10(-6) M) or substance P (2 x 10(-7) M) were significantly inhibited by the adenosine (3 x 10(-4) M) pretreatment. These data suggest that in isolated guinea pig bronchi adenosine selectively inhibits noncholinergic neurotransmission through prejunctional P1-purinoceptors.

ATP modulates the efferent function of capsaicin‐sensitive neurones in guinea‐pig isolated atria

“…Similar results have been obtained in another peripheral preparation, the guinea-pig bronchi by Kamikawa & Shimo (1989). In this preparation, electrical field stimulation induced a noncholinergic functional response due to substance P release, which was inhibited by both ATP and adenosine through prejunctional P1-purinoceptors.…”

Non‐adrenergic, non‐cholinergic neural activation stabilizes smooth‐muscle tone independently of eicosanoid factors in guinea‐pig isolated airways

“…However, when the resting tone was reduced in the distal trachea, we also observed a moderate contractile NANC component: this confirms the results of two recent studies (Belvisi et al, 1990;Linden et al, 1991a). In the guinea-pig main bronchus, on the other hand, the contractile NANC component appeared to dominate: this agrees with most previous studies (Andersson et al, 1983;Lundberg et al, 1983b;Frossard et al, 1987;Kamikawa & Shimo, 1989). In contrast, Grundstrom et al (1981) found no response to electrical field stimulation in the atropinized main bronchus, whereas Souhrada et al (1980) registered relaxant NANC response in this segment.…”

“…Kamikawa & Shimo (1989) demonstrated that the magnitude of the contractile NANC response depends on the level of passive tension prior to stimulation in guinea-pig isolated bronchi. We add to this previous data the finding that the level of active tension prior to stimulation, the resting tone, not only determines the magnitude of the NANC response but also appears to determine whether NANC neural activation leads to a relaxation or a contraction.…”

Purinergic Signaling in the Airways

“…ATP has been considered a NANC transmitter in inhibitory vagal nerves supplying the airways (Irvin et al, 1980(Irvin et al, , 1983Souhrada et al, 1980;Satchell, 1982;Pauwels et al, 1990). Adenosine inhibits NANC excitatory transmission in guinea pig trachea (Kamikawa and Shimo, 1989), in retrospect probably by acting on P1 (A 1 ) receptors on nerve terminal varicosities to inhibit transmitter release (Schmidt et al, 1995).…”