Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously shown that substance P (SP) regulates sphincter of Oddi (SO) motility in vivo. However, its mechanism of action remains unclear. Our aim was to develop an in vitro model to measure spikeburst (SB) an contractile frequency (CMC) of the SO and to characterize further SP effects. In 16 opossums, SO rings were excised, mounted within a Kreb's tissue bath with bipolar electrodes and force transducers, allowed to equilibrate, and exposed to increasing SP concentrations with washout between each test solution. Spikeburst and CMC frequencies were recorded on a polygraph, quantitated, expressed as differences before and during SP, and statistically analyzed with Student's test. Although SP induced a significant concentration-dependent increase in phasic SB frequency and CMC, the amplitude of concentrations was not affected by SP. A close correlation was found between basal and SP-stimulated SB and CMC, suggesting myoelectric and mechanical coupling. Previous exposure of SO to SP antagonist [D-Arg1, D-Pro2, D-Trp7,9, Leu11]-SP significantly decreased the response to SP. Tetrodotoxin (TTX), did not affect the delta CMC response to SP. In conclusion an in vitro preparation was developed to study the effect of SP on the SO. Substance P increased SB and CMC of the SO in a concentration-dependent fashion, thus acting as a stimulatory peptide. Perfusion of SO rings with SP antagonist had no effect on basal CMC but significantly inhibited the action of SP in a competitive manner. The effect of SP was not altered by TTX. These data suggest that the action of SP on the SO is primarily myogenic.
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PMID:Substance P stimulates the opossum sphincter of Oddi in vitro. 169 38

The interaction between bombesin and acetylcholine acting on smooth muscle of the stomach wall was investigated in two species of teleost fish. Oncorhynchus mykiss (rainbow trout) and Gadus morhua (Atlantic cod). Acetylcholine or bombesin alone has an excitatory effect on the stomach muscle. The effect on contraction amplitude of acetylcholine (10(-6)-10(-5) M) alone is about 10-times greater than the effect of bombesin (10(-9)-10(-7) M). In molar terms however, bombesin is more potent than acetylcholine. Bombesin (10(-8)-10(-7) M) added 0.5-3 min prior to acetylcholine potentiates the effect of acetylcholine in a dose-dependent manner. The potentiation is most pronounced in circular muscle preparations, but is present also in longitudinal muscle preparations. Bombesin affects the response to carbachol (10(-6) M) with a similar potentiation, indicating that the potentiation is not caused by inhibition of choline esterase activity. Atropine (10(-6)-10(-5) M) abolishes the response to bombesin plus acetylcholine as well as the response to acetylcholine alone. Tetrodotoxin (10(-6) M) does not block the effect of acetylcholine, bombesin or the combination acetylcholine plus bombesin. Substance P (10(-9)-10(-7) M) which has a similar excitatory effect on the stomach muscle as bombesin, does not potentiate the effect of acetylcholine. Immunohistochemistry has shown the presence of strong bombesin-like immunoreactivity in stomach nerves of the cod and weak bombesin-like immunoreactivity in rainbow trout nerves. In addition, bombesin-like immunoreactivity was demonstrated in endocrine cells in the gastric and intestinal mucosa of both species. It is concluded that bombesin, contained either in nerve fibres or in mucosal endocrine cells, specifically potentiates the effect of acetylcholine in the fish stomach.
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PMID:Bombesin potentiates the effect of acetylcholine on isolated strips of fish stomach. 170 14

1. The effects of scyliorhinins I (SCY I) and II (SCY II) on longitudinal (LM) and circular muscle (CM) strips isolated from the carp intestinal bulb were investigated in vitro and compared with that of substance P (SP). 2. SP (0.3 nM-1 microM), SCY I (0.3-300 nM) and SCY II (0.3 nM-1 microM) caused transient concentration-dependent contractions of LM strips. The EC50 values for SP, SCY I and SCY II were 16 nM, 15 nM and 39 nM, respectively. Tetrodotoxin and atropine partly decreased the contractile responses to SP, neurokinin A and neurokinin B, but did not change those to SCY I and SCY II. Spantide, methysergide, pyrilamine and naloxone did not decrease the contractile responses to SP, SCY I and SCY II. SP-induced desensitization selectively decreased the responsiveness of LM strips to SCY I and SCY II, and in addition, SCY I- or SCY II-induced desensitization decreased that to SP, SCY I and SCY II. 3. SP, SCY I and SCY II (1 nM-1 microM) caused concentration-dependent contraction of CM strips. The time course of the contractile response of CM strips was different from that of LM strips. Neither tetrodotoxin, atropine, methysergide nor spantide decreased the contractile responses to these tachykinins. 4. These results indicate that SCY I and SCY II act directly on tachykinin receptors located on smooth muscle cells and thus cause the excitatory response in the carp intestinal bulb.
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PMID:Excitatory responses to scyliorhinins I and II in smooth muscle strips isolated from the carp intestinal bulb (Cyprinus carpio). 171 22

The effects of ruthenium red, an inorganic dye with known capsaicin antagonist properties, was investigated in the rabbit eye. At a dose of 0.24 nmol ruthenium red inhibited the inflammatory effects of capsaicin (1 or 8 nmol). Unexpectedly, when the dye was injected in doses ranging from 0.24 to 7.4 nmol, it caused an inflammatory response with constriction of the pupil (miosis) and a breakdown of the blood-aqueous barrier, leading to a rise intraocular pressure. Tetrodotoxin (30 nmol) inhibited the ruthenium red-induced rise in intraocular pressure but had less effect on the miotic response. The tachykinin antagonist spantide inhibited the miosis but had no effect on the rise in intraocular pressure. Ruthenium red induced an increase in substance P-like immunoreactivity and calcitonin gene-related peptide-like immunoreactivity in the aqueous humor. These levels were positively correlated with the rise in aqueous humor protein concentration. The ruthenium red-induced miosis and, to a less extent, the rise in intraocular pressure were inhibited by the Ca2+ channel-blocking agent omega-conotoxin GVIA (CTX), indicating a partial dependence on an influx of extracellular Ca2+. CTX also attenuated the miotic effect of capsaicin but had no effect on the capsaicin-induced rise in intraocular pressure. It is concluded that, in the rabbit eye, ruthenium red induces a neurogenic inflammatory response besides its capsaicin antagonist effects.
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PMID:Ruthenium red and capsaicin induce a neurogenic inflammatory response in the rabbit eye: effects of omega-conotoxin GVIA and tetrodotoxin. 172 55

Preparations of rat descending colon mucosa have been used to record changes in short circuit current (SCC) under voltage clamp conditions. When added to the basolateral compartment capsaicin (8-methyl-N-vanillyl-6-nonenamide, 0.1-3 microM) caused an initial transient increase in SCC, followed by a more prolonged reduction in SCC, that lasted for 20-30 min. Repeated applications of 3 microM capsaicin caused desensitisation of the initial secretory response. The antisecretory effects (i.e. reduction in SCC from the original baseline) remained, although they were significantly reduced. In some preparations described as "non-responders", 3 microM capsaicin did not elicit a secretory response. No desensitization of the remaining antisecretory responses was observed in these tissues; in fact these reductions in SCC were consistently larger than those from tissues which responded with a secretory response. Tetrodotoxin (100 nM), hexamethonium (10 microM), and yohimbine (50 microM) had no significant effect upon either secretory or antisecretory responses. Ruthenium red (10 microM) abolished the secretory response to 3 microM capsaicin, but had no effect upon the antisecretory responses. Pretreatment of the tissues with 1 microM substance P (SP) resulted in significant desensitisation to the peptide and abolished the secretory response to 3 microM capsaicin. The antisecretory responses remained, and were significantly larger compared with responses from control tissues.
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PMID:The effects of capsaicin upon electrogenic ion transport in rat descending colon. 172 6

Peritonitis induced by serosal application of 0.1 M hydrochloric acid causes net fluid secretion via the enteric nervous system. The aim of the present study was to investigate the roles of vasoactive intestinal peptide (VIP) and tachykinins in this reflex(es). The release of tachykinins (substance P [SP], neurokinin A [NKA], neuropeptide K [NPK]) and VIP into the mesenteric circulation, net fluid transport, intestinal blood flow and sometimes motility were recorded simultaneously in extrinsically denervated jejunal segments of the cat in vivo. The release of both VIP and NKA was increased upon application of HCl to the cat jejunal serosa. Tetrodotoxin, hexamethonium and methionine enkephalin inhibited both the induced VIP release and the secretory response. The increased release of NKA was unaffected by hexamethonium. We propose that the intramural secretory reflex evoked by acid application of the serosa consists of an 'afferent' tachykinin neuron, a cholinergic interneuron and an 'efferent' VIPergic neuron innervating the secretory enterocytes.
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PMID:On the role of vasoactive intestinal polypeptide and tachykinins in the secretory reflex elicited by chemical peritonitis in the cat small intestine. 197 7

1. The mechanical responses to some autonomic drugs and neuropeptides of longitudinal muscle (LM) and circular muscle (CM) strips isolated from the carp intestinal bulb were investigated in vitro. 2. Acetylcholine and carbamylcholine caused concentration-dependent transient contraction of both LM and CM strips. Tetrodotoxin had no effect, but atropine selectively decreased the contractile responses to acetylcholine and carbamylcholine. 3. Excitatory alpha-2 and inhibitory beta adrenoceptors were present in both LM and CM strips. 4. 5-Hydroxytryptamine (5-HT) caused concentration-dependent contraction of both LM and CM strips. Tetrodotoxin, atropine and methysergide decreased the contractile responses to 5-HT. 5. Some neuropeptides (angiotensin I, angiotensin II, bombesin, bradykinin, neurotensin, somatostatin and vasoactive intestinal polypeptide) did not cause any mechanical response (contraction or relaxation) in either smooth muscle strip. 6. Substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) caused contraction of both LM and CM strips. However, the time course of the contraction in LM was different from that in CM. The order of potency was NKA greater than SP greater than NKB in LM strips and NKA greater than SP much greater than NKB in CM strips. In LM strips, the contractile responses to tachykinins were unaffected by spantide and methysergide, but partly decreased by tetrodotoxin and atropine. On the other hand, the contractile responses of CM strips were unaffected by tetrodotoxin, atropine, methysergide and spantide. 7. Dynorphin (1-13) (DYN), leucine-enkephalin (L-Enk) and methionine-enkephalin (M-Enk) caused concentration-dependent contraction of both LM and CM strips. The order of potency was DYN greater than M-Enk greater than L-Enk. Naloxone selectively decreased the responses to opiate peptides. 8. The present results indicate that acetylcholine, carbamylcholine, catecholamines, 5-HT, tachykinins (SP, NKA and NKB) and opiate peptides (DYN, L-Enk and M-Enk) affect the mechanical activity of LM and CM strips isolated from the carp intestinal bulb through their specific receptors.
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PMID:Effects of some autonomic drugs and neuropeptides on the mechanical activity of longitudinal and circular muscle strips isolated from the carp intestinal bulb (Cyprinus carpio). 198 39

The action of substance P (SP) on mucosal ion transport has been investigated in the guinea-pig small intestine. Segments of intestine were dissected free of external muscle and myenteric plexus and mounted in Ussing chambers. Short-circuit current (Isc) was measured as an indication of net ion transport across the tissue. SP (greater than 10(-10) M) added to the submucosal side of the tissue caused a transient increase in Isc. Tetrodotoxin (TTX, 10(-7) M) decreased the maximum SP response to 11% of the control value. TTX completely inhibited the response to electrical field stimulation but had no effect on Isc increases due to carbachol or theophylline. In the presence of hyoscine (10(-7) M) the SP response was reduced to 42% of the control value, but hyoscine had no effect on the TTX-resistant SP response. Mepyramine (10(-6)M) had no significant effect on the SP response. These results suggest that SP alters mucosal ion transport by stimulation of cholinergic and non-cholinergic nerves in the mucosa-submucosa. A small part of the SP response appears to be due to a direct action on epithelial cells. The SP antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP decreased the magnitude of the TTX-resistant SP response, and caused a decrease of similar magnitude in the total SP response. These results imply that the major component of the SP response, which is due to an action on neurons, is unaffected by this antagonist. It is concluded that the SP receptors on epithelial cells are blocked by the antagonist and are different to the SP receptors on submucous neurons, which are not blocked by the antagonist.
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PMID:Different substance P receptors are found on mucosal epithelial cells and submucous neurons of the guinea-pig small intestine. 241 39

Isometric tension was recorded from strips of bovine tracheal smooth muscle in which the tone had been artificially raised by agonist drugs such as histamine and carbachol. Application of exogenous acetylcholine produced a biphasic response consisting of an initial contraction followed by a more prolonged relaxation before tone was restored to normal. Atropine blocked both components of the biphasic response to exogenous acetylcholine. Tetrodotoxin blocked neither phase of the response to exogenous acetylcholine even though a similar biphasic response to electrical stimulation was severely disrupted. Application of exogenous substance P produced a biphasic response of similar magnitude and form to that produced by acetylcholine. Application of exogenous histamine (tone raised by carbachol) also produced a biphasic response although higher concentrations were required to produce a relaxation of equal magnitude to that produced by acetylcholine. It is concluded that the inhibitory component of the biphasic response to exogenous acetylcholine occurs as a non-specific sequel to contraction.
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PMID:Relaxation following contraction in tonically contracted smooth muscle from the bovine trachea. 241 66

Sensory transmission from the colon was studied using a preparation of inferior mesenteric ganglion (i.m.g.) attached to a segment of distal colon in guinea-pigs, in vitro. Electrical responses to colon distension were recorded intracellularly from neurones of the i.m.g. Distension of the distal colon up to an intraluminal pressure of 20 cmH2O caused an increase in resting asynchronous synaptic activity and a concomitant slow depolarization. The asynchronous synaptic activity, but not the slow depolarization, was abolished by cholinergic antagonists. Distension-induced non-cholinergic depolarizations were elicited in 44% of i.m.g. neurons sampled. For distensions of 1 min at 10-20 cmH2O, depolarizations reached a mean amplitude of 3.4 +/- 0.3 mV and lasted 108 +/- 7 s. Continuous distension resulted in a tachyphylaxis of the depolarization. Tetrodotoxin (3 X 10(-7) M) superfused over the i.m.g. reversibly abolished the distension-induced non-cholinergic depolarization. Distension-induced non-cholinergic depolarizations were accompanied by an increase in input resistance of 21%. Neuronal excitability also increased, as sub-threshold potentials produced by intracellular current injection reached threshold for firing action potentials during colon distension. The amplitude of non-cholinergic depolarizations increased with colonic intraluminal pressure between 2 and 20 cmH2O, although the slope of the mean amplitude-pressure curve decreased progressively at higher pressures. The amplitude of distension-induced non-cholinergic depolarizations increased as membrane potential was manually hyperpolarized to approximately -80 mV, whereupon further hyperpolarization resulted in a decrease in response amplitude. Non-cholinergic slow excitatory post-synaptic potentials (e.p.s.p.s) evoked by repetitive presynaptic nerve stimulation were reversibly attenuated by 19 +/- 8% during depolarizations produced by distension. Systemic administration of capsaicin (50-350 mg/kg) reduced the number of i.m.g. neurones exhibiting the non-cholinergic mechanosensory response; direct superfusion of capsaicin over the i.m.g. attenuated the response in some neurones but had no effect in others. These results demonstrate the existence of a non-cholinergic mechanosensory pathway from the colon to the i.m.g., and suggest that non-cholinergic transmission in the ganglion participates in mediating gastrointestinal reflexes. One transmitter utilized by the non-cholinergic mechanosensory pathway may be substance P.
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PMID:Non-cholinergic transmission in a sympathetic ganglion of the guinea-pig elicited by colon distension. 242 4


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