Evidence for the release of endogenous substance P from intestinal nerves

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. 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. 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. 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. 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. 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. 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. 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. 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.

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Effects of Substance P on Smooth Muscle Cells and on Neuro‐effector Transmission in the Guinea‐pig Ileum

Fujisawa¹,

Ito²

1982

“…Ample evidence, based on pharmacological, physiological, anatomical and neurochemical findings, indicates that tachykinins (TKs) play a physiological role as excitatory transmitters in the guinea-pig ileum (Franco et al, 1979;Costa et al, 1981;1985a,b;Bartho et al, 1982a,b;Donnerer et al, 1984;Llewellyn-Smith et al, 1988;Bartho et al, 1989;Holzer, 1989; see also Bartho & Holzer, 1985 for review). In the guinea-pig small intestine, substance P and other TKs, such as neurokinin A (NKA) are present (Too et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

Tachykininergic transmission to the circular muscle of the guinea‐pig ileum: evidence for the involvement of NK₂ receptors

Barthó

Santicioli

Patacchini

et al. 1992

1 The effect of newly developed, receptor-selective tachykinin antagonists (GR 71,251 for NK1 receptors, MEN 10,376 and L 659,877 for NK2 receptors) on noncholinergic transmission to the circular muscle of the guinea-pig ileum has been investigated. 2 In circular muscle strips of the ileum, electrical field stimulation in the presence of atropine (2 jM) and apamin (0.1 jAM) evoked a complex motor response. The tonic primary contraction in this response was reduced by GR 71,251 (10 jM) and MEN 10,376 (3-10 I1M) but not by L 659,877 (up to 10 jM). The presence of apamin was necessary in this experimental arrangement to unmask an atropine-resistant primary contraction, sensitive to tachykinin antagonists. The motor response was abolished by tetrodotoxin.3 In circular strips of the ileum GR 71,251 (10 jM) inhibited the tonic contraction produced by [Sar9] substance P sulphone, a selective NK1 receptor agonist but not that produced by [,B Alal] neurokinin A (4-10), a selective NK2 receptor agonist. By contrast, MEN 10,376 antagonized the effect of the NK2 agonist while leaving the response to the NK, agonist unaffected. 4 In whole segments of the ileum, distension of the gut wall by an intraluminal balloon placed at about 1 cm from the point of recording of mechanical activity of the circular muscle produced atropinesensitive phasic contractions (ascending enteric reflex). In the presence of atropine (2 jiM), a noncholinergic response was elicited, which required larger volumes of distension that the cholinergic one. The atropine-resistant ascending enteric reflex was enhanced by apamin (0.1 j1M) and abolished by tetrodotoxin, either in the presence or absence of apamin. 5 MEN 10,376 (3-lOM) inhibited the atropine-resistant ascending enteric reflex in the presence of apamin while GR 71,251 or L 659,877 (10 lM each) were ineffective. MEN 10,376 inhibited the atropine-resistant ascending enteric reflex to a larger extent in the absence than in the presence of apamin and also slightly inhibited the ascending enteric reflex in the absence of atropine. 6 These findings provide evidence for an involvement of NK2 tachykinin receptors in excitatory transmission to the circular muscle of the guinea-pig ileum. NK2 receptors are also involved in the physiological-like circular muscle activation produced by stimulation of intramural neuronal pathways which subserve the atropine-resistant ascending enteric reflex.

“…Ample evidence, based on pharmacological, physiological, anatomical and neurochemical findings indicates that tachykinins (TKs) play a physiological role as excitatory transmitters in the guinea-pig ileum (Franco et al, 1979;Costa et al, 1981;Donnerer et al, 1984;Llewellyn-Smith et al, 1988;1989;Bartho' et al, 1989;Holzer, 1989; see also Bartho' & Holzer 1985 for review). In the guinea-pig intestine, substance P (SP) and other TKs, such as neurokinin A (NKA) (Too et al, 1989) are stored in intrinsic neurones thought to play a role as final effectors of the atropine-resistant peristalsis (Bartho' & Holzer, 1985 for review).…”

Section: Introductionmentioning

confidence: 99%

Tachykinin receptors in the circular muscle of the guinea‐pig ileum

Maggi

Patacchini

Giachetti

et al. 1990

The response to the selective NK2-agonist was unchanged after desensitization of NK1-or NK3-receptors.6 The response to the NK2-selective agonist was strongly inhibited by [Tyr5,8'9, Argl0]-NKA(4-10) (MEN 10,207) a selective NK2-receptor antagonist which did not modify the response to the NK1-selective agonist. 7 Our findings indicate that all the three known types of tachykinin receptors mediate the contractile response of the circular muscle of the guinea-pig ileum to peptides of this family. The response to activation of NK3-receptors is totally neurogenic and partially mediated by endogenous acetylcholine, the response to activation of NK1-receptors is partly neurogenic and largely myogenic and the response to activation of NK2-receptors is totally myogenic.