DIFFERENCES IN THE EFFECTS OF TACHYKININ NK(1) RECEPTOR ANTAGONISTS -NEURONAL VERSUS SMOOTH-MUSCLE TISSUES

The effects of three tachykinin NK1 receptor antagonists (L-668,169, ( +/-)-RP 67580, and (+/-)-CP 96.345) were examined for their ability to antagonise responses evoked by substance P 0-methyl ester (a selectiv e NK1 receptor agonist) in isolated neuronal tissue (rat superior cerv ical ganglia and guinea-pig locus coeruleus) and smooth muscle tissues (rat urinary bladder and guinea-pig ileum longitudinal muscle/myenter ic plexus). ( +/- )-RP 67580 was similarly effective in antagonising r esponses in both rat superior cervical ganglia and urinary bladder (es timated pK(a) value = 7.4 for both tissues); however, ( +/- )-CP 96,34 5 was 50-fold less effective in antagonising responses in guinea-pig l ocus coeruleus than in ileum longitudinal muscle/myenteric plexus (est imated pK(a) values = 7.6 and 9.3 respectively). It is suggested that the differential effects of ( +/- )-CP 96,345 may reflect the existenc e of a population of NK1 receptors within guinea-pig locus coeruleus t hat are less sensitive to the effects of this NK1 receptor antagonist.