Dual effect of (−)‐N⁶‐phenylisopropyl adenosine on guinea‐pig trachea

Abstract

(via P2-purinoceptor?). Thus the balance between the two opposite effects of adenosine on tracheal tone is possibly modulated by the prostaglandin turnover.

Effects of NZ-107 on Tracheal Responses to Adenosine in the Guinea Pig.

“…Since the cyclooxygenase inhibitor in domethacin completely inhibited R-PIA-in duced contraction, it is suggested that the con tractile response elicited by R-PIA is mediated by cyclooxygenase metabolites, such as con strictor PGs. Similar results have been re ported by Farmer et al (18) and Caparrotta et al (19). Since NZ-107 (1 ,uM) significantly in hibited the contraction induced by PGF2a, it is suggested that NZ-107 reduces R-PIA-induced contraction by inhibiting the contraction in duced by endogenously released PGF2a.…”

“…In guinea pig trachea, adenosine-in duced relaxation is reported to be mediated by A2 receptors (16,17). The stable adenosine analogue R-PIA, which is relatively selective for adenosine Al receptors (14), elicits a con tractile response in guinea pig trachea at con centrations lower than about 1 uM (18,19). In the present study, adenosine caused only relaxation at concentrations higher than 3 uM, and R-PIA caused contraction at concentra tions less than 1 u M, suggesting that adeno sine and R-PIA act on A2 and Al receptors, respectively, in the guinea pig trachea.…”

Adenosine receptor‐mediated contraction and relaxation of guinea‐pig isolated tracheal smooth muscle: effects of adenosine antagonists

“…The relaxation of guinea-pig trachea to adenosine may be mediated by A2-adenosine receptors (Brown & Collis, 1982). Caparrotta et al (1984) found that the stable adenosine analogue, Rphenylisopropyladenosine (R-PIA), at concentrations lower than 1 um, elicited a contractile response in guinea-pig trachea, an effect which was blocked by indomethacin. Since R-PIA is relatively selective for adenosine A,-receptors (Daly, 1982;Burnstock & Buckley, 1985), the contractile response may be mediated by this receptor subtype.…”

Contraction of the rat isolated spleen mediated by adenosine A1 receptor activation

“…Such a mechanism in the splenic capsular smooth muscle would provide a plausible explanation for the contractile response in the present study; it would also be entirely consistent with the observation that suppression of calcium influx through L-calcium channels had minimal effects on contraction induced by R-PIA (Figure 4d). In cat lung and guinea-pig uterus and trachea, responses mediate by A1 receptor stimulation are markedly attenuated by inhibitors of cyclo-oxygenase (Caparrotta et al, 1984;Neely et al, 1991;Schiemann et al, 1991a) suggesting that smooth muscle contraction in these tissues may be secondary to the synthesis of prostaglandins from arachidonic acid. In contrast to these findings, a substantial component of the contraction of the spleen induced by R-PIA was resistant to blockade by indomethacin (10-6M), a concentration sufficient to inhibit cyclo-oxygenase (Tolman & Partridge, 1975).…”

“…Adenosine and several closely related analogues induce contraction of both vascular and non-vascular smooth muscle including the resistance vessels of rat kidney (Kenakin & Pike, 1987) and cat lung (Neely et al, 1991), guinea-pig trachea (Advenier et al, 1982;Caparrotta et al, 1984;Ghai et al, 1987;Farmer et al, 1988), myometrium (Smith et al, 1988) and aorta (Stoggall & Shaw, 1990) and both the muscularis mucosa and the longitudinal muscle of the rat colon (Bailey & Hourani, 1990;Bailey et al, 1992). Evidence obtained with both agonists and antagonists implicates the adenosine Al receptor in these responses although such analyses have been complicated by the presence of other purinoceptor subtypes mediating both contraction and relaxation in these tissues.…”