Characterisation of receptors mediating the contractile effects of prostanoids in guinea-pig and human airways

Prejunctional prostanoid receptors on cardiac adrenergic terminals belong to the EP3 subtype

“…The present study has confirmed our previous observation 0 -g 0 that PGE2 is able to reduce the response to sympathetic nerve stimulation in guinea-pig atria (Mantelli et al, 1990 (Coleman et al, 1987a;1987b;Coleman, 1988 On the other hand, the inhibitory effect of the EP agonists did not seem to be mediated by EP1 receptors since AH6809, an antagonist able to block the effects mediated by EP1 receptors (Coleman et al, 1985;McKenniff et al, 1988) Agonist concentration (nM) Figure 4 Effect of prostaglandin E2 (PGE2) and sulprostone, alone and in the presence of AH6809, on the cardiac response to field stimulation in guinea-pig isolated atria: (0) PGE2 alone (n = 5); (0) PGE2 in the presence of 1UM AH6809 (n = 4); (U) sulprostone alone (n = 4); (El) sulprostone in the presence of 1pM AH6809 (n = 4).…”

BAY u3405 an antagonist of thromboxane A2‐ and prostaglandin D2‐induced bronchoconstriction in the guinea‐pig

“…Although the limited activity of GR 32191 may simply reflect low potency, it might alternatively reflect limited activity against all TXA2 receptor subtypes. McKenniff et al (1988McKenniff et al ( , 1991 have suggested that subtypes of TXA2 receptors exist in airway smooth muscle. They have demonstrated that some TXA2 antagonists, including GR 32191, were not equipotent at all such subtypes.…”

“…The contractile activity of TXA2 and PGD2 on airway tissues is well documented (Coleman et al, 1980;Black et al, 1986;McKenniff et al, 1988;Giles & Leff, 1988). The metabolite of PGD2 (9a, 1 1fJ-PGF2) also has potent contractile activity on human and guinea-pig airways in vitro (Featherstone et al, 1990) and by inhalation in man (Beasley et al, 1987).…”

Using guinea pigs in studies relevant to asthma and COPD

“…Exceptions to the predictive value of guinea pig airway receptor pharmacology for that of humans include the expression of a cysLT 2 -like leukotriene receptor on guinea pig airway smooth muscle but not on human airway smooth muscle, and the expression of neurokinin 1 receptors and contractile prostanoid EP 1 receptors on the airway smooth muscle in guinea pigs but not in human airway smooth muscle [19,55,57,[250][251][252][253]. Serotonin also contracts guinea pig (and mouse and rat) airway smooth muscle but not that of humans [21].…”