Substance P can contract the longitudinal muscle of the guinea‐pig small intestine by releasing intracellular calcium

Abstract

1 The contraction of the longitudinal muscle of the guinea-pig isolated ileum in response to substance P (SP) in high [K+] 3 Bathing the ileum in a Ca2+-free medium for 2.5 min greatly diminished the potency and efficacy of SP in contracting the longitudinal muscle but concentrations of 2.2-22 tLM SP were still able to produce a response 30-40% of maximal. 4 The responsiveness to SP was completely lost within 10 min of bathing in Ca2+-free medium but was partially restored by a brief exposure (0.5 -2 min) to high concentrations of Ca2+ (9-72 mM). The restorative effect of Ca2+ depended on the concentration of Ca2+ and on the time for which the tissue was exposed to this Ca2+ concentration. 5 The fact that high concentrations of SP were able to elicit a contraction in media containing high [K+] or no Ca2+, suggested that they may do so by releasing Ca2+ from an intracellular store which is not as sensitive to removal of extracellular Ca2+ or as easily accessible to EGTA as the extracellular space of the muscle. The location of this store is not known; it may be associated with the internal side of the cell membrane. 6 There is apparently an overlap between the Ca2+ pool associated with the action of SP and the Ca2+ pools utilized by acetylcholine, histamine or tetraethylammonium, which accounts for the cross-desensitization observed between these agonists. It was not possible to determine whether autodesensitization to SP also results from depletion of an intracellular Ca2+ store.

Inhibitory Effect of Octopamine on the Release of Endogenous Acetylcholine From Isolated Myenteric Synaptosomes of Guinea‐pig

“…In the control experiments, we employed substance P to induce the release of endogenous ACh from myenteric synaptosomes of guinea-pig ileum. Substance P works as an excitatory neurotransmitter in guinea-pig ileum (Franc0 et al 1979) via the release of ACh from myenteric plexus (Yau & Youther 1982) and the direct contraction of intestine (Holzer & Lippe 1984). Our results are in agreement with the previous view (Holzer & Lembeck 1980) that substance P induced the Cadependent release of ACh from myenteric plexus.…”

Dopamine‐induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea‐pig mediated via α‐adrenoceptors

“…In the control experiments, we confirmed that substance P induced a concentrationdependent release of endogenous ACh in guinea-pig ileum synaptosomes. Substance P works as an excitatory neurotransmitter in guinea-pig ileum (Franco, Costa & Furness, 1979) via the release of ACh from myenteric plexus (Yau & Youther, 1982) and/or the direct contradiction of intestine (Holzer & Lippe, 1984). Our results agree with the previous view (Holzer & Lembeck, 1980) that substance P induced the Cazf-dependent release of ACh from the myenteric plexus.…”

Chronic treatment with fluoride affects the jejunum: insights from proteomics and enteric innervation analysis

“…Many proteins observed in the previous study were correlated with the neurotransmission process, which is essential for the function of the GIT through ENS control. For example, the pattern of intestinal smooth muscle contraction can be modified when the release of neurotransmitters stimulating muscle contraction, such as SP 26 is increased or when the release of neurotransmitters promoting muscle relaxation, such as NO 27 , is decreased. In the present study, both conditions might have occurred, because we found a significance increase and decrease in the mean values of the SP varicosities area and the density of nNOS-IR neurons, respectively (Table 1 ), which is in accordance with our previous findings for the duodenum 13 .…”