Abstract
1 The effects of substance P (SP) on the membrane and contractile properties of the smooth muscle cell, or on neuro-effector transmission in the guinea-pig ileum were observed by means of microelectrodes, double sucrose gap and tension recording. 2 SP (10−13-10−10 M) induced a phasic contraction of longitudinal muscle strips, but did not change the muscle tone of circular muscle strips, in concentrations up to 10−8 M. 3 SP (1010-10-8M) evoked three different membrane responses in longitudinal muscle cells: (i) bursts of spike discharges with no significant change in the membrane potential and input membrane resistance; (ii) bursts of spike discharges with a small but clear depolarization of the membrane and increase in the input membrane resistance; (iii) slow waves with no change in the membrane potential. 4 In the circular muscle cells, low concentrations of SP (< 10−8M) did not affect the membrane potential or the spikes, but SP (10−7M) increased the spike discharges with no significant change in the membrane potential. 5 SP (10−10M) reduced the threshold depolarization required for the generation of action potentials with no change in membrane potential of the longitudinal muscle cells. 6 Pretreatment with atropine (5 × 10−6M), tetrodotoxin (TTX 10−6M) or baclofen (4.7 × 10−6M) had no effect on the excitatory actions of SP on the smooth muscle cells of longitudinal and circular muscle strips. 7 Excitatory actions of SP on the membrane potential or spike activities of longitudinal muscle cells were preserved in NaCl but not in Ca-deficient solution. 8 SP (10−10-10−9M) enhanced the amplitude of the excitatory junction potentials (e.j.ps) evoked by electrical field stimulation in longitudinal muscle cells with no change in the membrane potential and input resistance. SP (10−10-10−9M), however, did not change the amplitude of inhibitory junction potentials (i.j.ps) recorded from the circular muscle cells. 9 These results indicate that SP in relatively low concentrations acts on both smooth muscle cells and on excitatory neuro-effector transmission in the longitudinal muscle; the main site of the action of SP is probably the muscle membrane.