The nature of non-cholinergic, non-adrenergic transmission in longitudinal and circular muscles of the guinea-pig ileum.

1. The nature of the non-cholinergic, non-adrenergic (non-ch., non-adr.) excitatory and inhibitory transmission in the longitudinal and circular muscle layers of the guinea-pig ileum was investigated, and the effects of various agents on the junction potentials were observed using the micro-electrode method.2. In longitudinal muscle cells, ATP (3 x 10(-5)-10(-4) M) and adenosine (10(-5)-10(-4) M) depolarized the membrane, decreased the input resistance, increased the spike activity and abolished the generation of cholinergic excitatory junction potentials (e.j.p.s).3. In the presence of atropine (10(-6) M) with guanethidine (10(-5) M), field stimulation evoked three different types of the response (non-ch., non-adr. e.j.p.s, i.j.p.s (inhibitory junction potentials) or both) from cells of the longitudinal muscle layers, and only one type of the response (non-ch., non-adr. i.j.p.s) from cells of the circular muscle layer. In the following experiments atropine and guanethidine were present in the bathing fluid for at least 20 min.4. In some longitudinal muscle cells (non-ch., non-adr. i.j.p. type), ATP (5 x 10(-6)-10(-3) M) and adenosine (10(-5)-3 x 10(-5) M) depolarized the membrane, while in other cells (non-ch., non-adr. e.j.p. type), ATP (10(-5)-10(-4) M) and adenosine (10(-5)-3 x 10(-5) M) hyperpolarized the membrane and further increases in the concentration of ATP (10(-3) M) resulted in a depolarization of the membrane.5. Apamin (10(-7)-3 x 10(-6) M) inhibited the generation of non-ch., non-adr. i.j.p.s in both longitudinal and circular muscle cells, while this agent had no effect on the non-ch., non-adr. e.j.p.s. As a consequence, in some cells of the longitudinal muscle layer (non-ch., non-adr. e.j.p. and i.j.p. type) the amplitude of e.j.p.s was enhanced in the presence of apamin. TEA (5 x 10(-3)-1.5 x 10(-2) M) suppressed the after-hyperpolarization of the spike and i.j.p.s recorded from both muscle layers, whereas the duration and amplitudes of cholinergic and non-ch., non-adr. e.j.p.s were enhanced.6. Vasoactive intestinal polypeptide (VIP; 10(-8)-10(-7) M) had no effect on the membrane potential and junction potentials of longitudinal and circular muscle layers.7. Substance P (SP; 10(-8)-10(-7) M) depolarized the membrane of cells of the longitudinal layer (non-ch., non-adr. e.j.p. type), while this agent had no effect on cells of longitudinal (non-ch., non-adr. i.j.p. type) and circular muscle layers. SP suppressed the generation of non-ch., non-adr. e.j.p.s but had no effect on i.j.p.s. Generation of non-ch., non-adr. e.j.p.s was not restored under conditions of repolarization of the membrane to the resting level by application of inward current.8. Bradykinin (BK; 10(-8)-10(-5) M) hyperpolarized the membrane and suppressed the generation of i.j.p.s in the cells of longitudinal (non-ch., non-adr. i.j.p. type) and circular muscle layers. However, when the membrane potential was displaced to the control level by outward current in the presence of BK, field stimulation evoked the i.j.p. In cells of non-ch., non-adr. e.j.p. type of the longitudinal muscle layer, BK depolarized the membrane, increased the spike activity, generated slow waves and blocked the generation of non-ch., non-adr. e.j.p.s. Displacement of the membrane potential to the control level by inward current did not restore the non-ch., non-adr. e.j.p.s.9. These results suggest that in the guinea-pig ileum ATP and adenosine probably do not contribute to the generation of non-ch., non-adr. e.j.p.s and i.j.p.s, as transmitter substances. The actions of other possible candidates such as SP and BK, are discussed.