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)

1. Intracellular recordings were made from neurones of the guinea-pig gall-bladder in vitro. Intracellular injection of horseradish peroxidase revealed a simple structure, consisting of a soma and a single process, but no discernible dendritic arborization. 2. The resting membrane potential was -50.5 +/- 0.4 mV and the input resistance was 80 M omega. 3. Gall-bladder neurones spiked only once at the onset of depolarizing current pulses. Action potentials were blocked by tetrodotoxin, but a Ca2(+)-dependent spike could be elicited in the presence of tetrodotoxin and tetraethylammonium. 4. Action potential after-hyperpolarizations had a duration of 172 +/- 3.7 ms and reversed at a membrane potential of -93 mV; this reversal potential was linearly related to the logarithm of the external potassium concentration. The initial phase of the after-hyperpolarization was inhibited by tetraethylammonium (1-10 mM) and was not affected by 3,4-diaminopyridine. The late phase of the after-hyperpolarization was blocked by apamin (10 nM) or curare (500 microM). Both the early and late phases of the after-hyperpolarization were inhibited when the preparation was perfused with a calcium-free, high-magnesium solution. The calcium-free, high-magnesium solution had no effect on the membrane potential or input resistance of these cells. 5. Fast excitatory synaptic responses and antidromic responses were elicited in gall-bladder neurones by focal stimulation of fibre tracts. High-frequency fibre tract stimulation often resulted in prolonged, calcium-dependent, depolarizations that were associated with a decrease in input resistance. 6. 5-Hydroxytryptamine and substance P caused depolarizations that were associated with a decrease in input resistance. Bethanechol caused hyperpolarizations that were associated with a decrease in input resistance and which were blocked by atropine.
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PMID:Intracellular recording from neurones of the guinea-pig gall-bladder. 170 71

The actions of the macrolide antibiotic, erythromycin lactobionate (EM), on nerve-mediated and drug-induced contractions of longitudinal and circular muscle of guinea pig small intestine were studied in vitro. Longitudinal muscle contractions, evoked by single transmural electrical stimuli, were inhibited by EM (10-300 microM) with half-maximal inhibition occurring at 161 microM (EC50). EM-induced inhibition of longitudinal muscle contractions was not affected by the alpha-2 adrenergic antagonist, yohimbine (0.3 microM), by the adrenergic neuronal blocker, guanethidine (10 microM), or the opiate receptor antagonist, naloxone (1.0 microM). Bethanechol-induced longitudinal muscle contractions were also reduced by EM. Noncholinergic longitudinal muscle contractions (1 microM scopolamine present), induced by trains of transmural stimuli, were reduced by EM (EC50, 142 microM); substance P (a mediator of noncholinergic contractions)-induced contractions were also reduced by EM. Circular muscle contractions, evoked by brief trains of transmural stimulation, were inhibited by EM but bethanechol- and substance P-induced contractions of the circular muscle were not altered by EM. Segments (2 cm) of small intestine were used to study reflex circular muscle contractions evoked by distention of the segment aboral to the recording point. Reflex contractions were inhibited by EM (EC50, 84 microM). These data indicate that, in the guinea pig small intestine, EM inhibits nerve-mediated contractions by actions on enteric nerves and on longitudinal but not circular muscle.
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PMID:Erythromycin inhibits contractions of nerve-muscle preparations of the guinea pig small intestine. 204 26

To determine whether serous or mucous cells in tracheal submucosal glands respond to the neuropeptides substance P (SP) and vasoactive intestinal peptide (VIP), we studied the peptide-induced changes in gland cell morphology accompanying release of 35SO4-labeled macromolecules from tracheal explants of ferrets. Explants were labeled for 1 h in medium containing 35SO4 and washed for 3.5 additional hours. Base-line secretion in the absence of drugs declined between 1.5 and 3.5 h after the pulse. Between 2.5 and 3.5 h, the average percent change in counts per minute recovered per sample period was not significantly different from zero (P greater than 0.3; n = 6). Substance P (10(-5) M) and VIP (2 X 10(-6) M) added 4 h after labeling each increased greatly the release of 35SO4-labeled macromolecules (SP, 219%; VIP, 180%) above base line. Bethanechol, a muscarinic-cholinergic agonist (10(-5) M), increased secretion by an average of 142% above base line (each effect, P less than 0.05; n = 6 each). Light and electron microscopy of the control tissues showed glands with narrow lumens and numerous secretory granules. Glands treated with SP or VIP had enlarged lumens and the serous cells were markedly degranulated. These phenomena were documented by morphometry and suggest that SP and VIP cause secretion from glands at least partially by stimulating exocytosis from serous cells.
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PMID:Neuropeptides degranulate serous cells of ferret tracheal glands. 242 58

The purpose of this study was to determine the intrinsic functions of the feline pylorus in vitro. The myoelectric and pressure characteristics of the intact pylorus, antrum, and duodenum, free of extrinsic hormonal or neural influences, were studied in an in vitro bath that allowed separation of the bathing medium surrounding the different bowel segments. Basal recordings revealed a zone of tonic high pressure of 28.4 +/- 3.5 mmHg (mean +/- SEM) at the pylorus. The basal slow wave frequencies in the pylorus and duodenum were 2.8 +/- 1.4 and 12.6 +/- 0.6 cycles/min, respectively. Spontaneous action potential-associated phasic contractions of the pylorus were noted in 38% of preparations. Enteric nerve stimulation with direct electric current (10 Hz, 1 ms, 10-50 V) applied proximal to the pylorus gave relaxation of the pylorus at the lower voltages and rebound excitation at higher voltages. Electrical stimulation distal to the pylorus yielded phasic contractile pyloric response during the entire stimulus. The duodenal instillation of 0.5 N HCl produced action potential-associated phasic contractions of the pylorus and duodenum but not the antrum. Pyloric responses to electrical stimulation or acidification were abolished by tetrodotoxin (10(-5) M). Bethanechol (10(-6) M) or substance P (10(-7) M) produced a contractile response at the site of stimulation but this response was not transmitted to include adjacent bowel segments. These studies suggest that the pyloric sphincter with its intrinsic reflex properties can be studied in vitro.
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PMID:Properties of the feline pyloric sphincter in vitro. 243 69

We studied smooth muscle strips from rabbit proximal stomach to explore the age-related changes in agonist-mediated contraction. Strips from neonatal (1 d) and weanling (11 wk) rabbits were oriented to measure isometric tension in circular muscle. Bethanechol stimulated maximal tension in both age groups. Although the potencies for bethanechol were similar (ED50 approximately 5 microM), the maximal response was nearly 4-fold greater in weanling (1140 +/- 73 mN/cm2) versus neonate (305 +/- 54 mN/cm2), p less than 0.001. Maximum stress increased with age for bethanechol, high extracellular K+, and substance P, but not for serotonin, cholecystokinin octapeptide, neurotensin, or bombesin. Only bombesin stimulated larger contraction in neonates (152 +/- 37 mN/cm2) versus weanlings (86 +/- 20 mN/cm2), p less than 0.05. Potencies did not change with age, except for substance P and serotonin. Substance P and serotonin induced early phasic and prolonged tonic contractions, which were unaffected by tetrodotoxin or atropine. ED50 for the phasic and tonic components of substance P-stimulated contraction in neonates were 1.8 and 7.7 nM. Substance P was 60-70 times more potent in neonates versus weanlings (p less than 0.001). ED50 for serotonin-stimulated contraction in neonates (33 and 22 nM, respectively) were 20-30 times more potent than in weanlings (p less than 0.05). Motilin, morphine, epidermal growth factor, and gastrin did not stimulate contraction at either age. We conclude that age-dependent changes in agonist potency and efficacy may be one factor to explain in part the changes that occur in gastric motility during postnatal development.
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PMID:Developmental changes in agonist-mediated gastric smooth muscle contraction in the rabbit. 247 52

Nitric oxide (NO) mediates neurogenic relaxations of gastrointestinal (GI) smooth muscle. NO synthase (NOS) inhibitors also alter neurogenic contractions, suggesting NO modulates excitatory neurotransmitter release. In circular muscle-myenteric plexus preparations, guanethidine and either scopolamine or CP-96,345, a neurokinin-1 (NK1) receptor antagonist, were used to isolate nonadrenergic, noncholinergic (NANC) or cholinergic contractions, respectively. NOS inhibitors and hemoglobin potentiated neurogenic NANC but not cholinergic contractions and did not affect NK1 receptor agonist [substance P methyl ester (SPME)]-induced contractions. Sodium nitroprusside (SNP), a NO donor, attenuated NANC and cholinergic neurogenic contractions, but cholinergic contractions were less sensitive to SNP. SNP partially attenuated SPME-induced contractions, and apamin reduced inhibition of NANC contractions by SNP. Bethanechol responses were not affected by SNP. These data indicate NANC but not cholinergic contractions are inhibited by endogenous NO, suggesting differential regulation of release of tachykinins and acetylcholine from enteric nerves. NK1 receptor-but not muscarinic receptor-activated postjunctional pathways are also inhibited by NO. Therefore, prejunctional and postjunctional modulation of NANC contractions are mechanisms for inhibition of GI motility by endogenous NO.
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PMID:Endogenous NO inhibits NANC but not cholinergic neurotransmission to circular muscle of guinea pig ileum. 894 6

Little is known about the acute and chronic effects of the intestinal transplantation on smooth muscle contractile physiology. Our aim was to determine the effects of the denervation necessitated by jejunoileal autotransplantation on membrane potential and contractile activity. Six dogs underwent a model of jejunoileal autotransplantation that specifically avoids ischemia/reperfusion injury (by maintaining blood flow to the gut during the "transplantation" procedure). Strips of jejunal circular muscle were studied sequentially before and 2 and 8 weeks after denervation by recording mechanical and intracellular electrical activities in vitro. The amplitude of spontaneous contractions (X +/- SD) was increased (P < 0.05) at 2 compared to 0 weeks (126 +/- 19 vs 77 +/- 32 g/g; P < 0.05) but markedly decreased at 8 weeks (7 +/- 2 g/g). Contraction frequency, resting membrane potential, and amplitude of slow waves were unchanged across these time points. Bethanechol (10(-7)-10(-4) M) and substance P (10(-8)-10(-6) M) dose-dependently increased contractile activity at all time points, but the absolute change in amplitude was decreased at 8 weeks. The amplitude of inhibitory junction potentials (IJPs) and duration of inhibition of contractile activity in the presence of cholinergic and adrenergic blockade increased at 2 and 8 weeks; off-contraction amplitude was decreased at 8 weeks (P < 0.05). These effects may occur via changes in neurotransmitter release, changes in regulation of membrane receptors, or alteration of characteristics of the membrane threshold potential.
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PMID:Effect of extrinsic denervation in a canine model of jejunoileal autotransplantation on mechanical and electrical activity of jejunal circular smooth muscle. 900 14

The trefoil factor TFF3 is a peptide predominantly produced by mucus-secreting cells in the small and large intestines. It has been implicated in intestinal protection and repair. The mechanisms that govern TFF3 secretion are poorly understood. The aim of this study was, therefore, to evaluate the influence of neurotransmitters, hormonal peptides and mediators of inflammation on the release of TFF3. For this purpose, an isolated vascularly perfused rat colon preparation was used. After a bolus administration of 1 ml isotonic saline into the lumen, TFF3 secretion was induced by a 30-min intra-arterial infusion of the compounds to be tested. TFF3 was evaluated in the luminal effluent using a newly developed radioimmunoassay. TFF3 was barely detected in crude luminal samples. In contrast, dithiothreitol (DTT) treatment of the effluent revealed TFF3 immunoreactivity, which amounted to about 0.3 pmol min(-1) cm(-1) in the basal state. Gel chromatography of DTT-treated luminal samples revealed a single peak that co-eluted with the monomeric form of TFF3. TFF3 was not detected in the portal effluent. Bethanechol (10(-6)-10(-4) M), vasoactive intestinal peptide (VIP, 10(-8)-10(-7) M) or bombesin (10(-8)-10(-7) M) induced a dose-dependent release of TFF3. In contrast, substance P evoked a modest release of TFF3, whereas calcitonin gene-related peptide (CGRP), somatostatin, neurotensin or peptide YY (PYY) did not modify TFF3 secretion. The degranulator compound bromolasalocid, 16,16-dimethyl PGE2 (dmPGE2) or interleukin-1-beta (IL-1-beta) also evoked a marked release of TFF3. In conclusion, TFF3 in the colonic effluent is present in a complex. This association presumably involves a disulfide bond. Additionally, the present results suggest a role for enteric nervous system and resident immune cells in mediation of colonic TFF3 secretion.
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PMID:Secretion of the trefoil factor TFF3 from the isolated vascularly perfused rat colon. 1149 77