FURTHER-STUDIES ON THE EFFECTS OF SELECTIVE NEUROKININ AGONISTS UPON THE ACTIVATION OF MICTURITION REFLEX IN RATS - EVIDENCE FOR A DUAL NK-1 RECEPTOR-MEDIATED EXCITATORY AND INHIBITORY ACTIVITY

The ability of SP and some selective agonists for NK-1, NK-2 and NK-3 receptor subtypes to interfere with the micturition reflex after intra -arterial (i.a.) or intracerebroventricular (i.c.v.) administration wa s investigated in the urethane anaesthetized rat. When administered i. a. SP, the selective NK-1 agonist GR 73632 and the selective NK-2 agon ists GR 64349 were equipotent to activate micturition reflex, both the tonic or rhythmic bladder contractions. GR 73632 but not GR 64349-ind uced activation of micturition reflex was antagonized in a dose-depend ent manner by the selective NK-1 antagonist GR 82334. After i.c.v. adm inistration SP, GR 73632 and the selective NK-1 agonist [Sar9,Met(02)1 1]-SP but not GR 64349 inhibited saline-induced activation of rhythmic bladder contractions; the order of potency was GR 73632 > [Sar9,Met(0 2)11]SP > > SP. Also the inhibitory effect of GR 73632 was dose-depend ently affected by GR 82334. In the two models the selective NK-3 agoni st senktide both after i.a. or i.c.v. administration induced neither e xcitatory or inhibitory activity. These findings suggest that neurokin ins activate at the peripheral level the micturition reflex by an inte raction at NK-1 and NK-2 receptor subtypes. In addition, NK-1 receptor s appear to modulate, at the central level, the inhibition of the mict urition reflex.