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)

This study was undertaken to assess whether a hypothalamic extract has any direct metabolic action on adipose and muscle tissues. An acid bovine hypothalamic extract (HE) was tested for its effect on the utilization of D[U-14C]glucose by isolated rat adipocytes and rat hemidiaphragms. The HE was ineffective in stimulating the conversion of labeled glucose into CO2 and glycogen by rat hemidiaphragm. However, in isolated adipocytes, the HE had significant lipogenic activity. This lipogenic effect was independent of insulin and nonsuppressible by insulin antibodies. The dose-response curve was linear and saturable. That insulin and the HE were not additive at maximal concentrations suggests that they act through a common rate-limiting step, possibly a receptor site. Other hypothalamic substances tested (thyrotropin-releasing hormone, luteinizing hormone-releasing hormone, and substance P) showed no lipogenic activity. Somatostatin (6 microgram/ml) was an insulin potentiator but only when preincubated with the fat cells. It is concluded that the hypothalamic regulation of body weight may be mediated by a neurohumoral mechanism affecting adipose tissue stores.
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PMID:Effect of a bovine hypothalamic extract on glucose utilization by rat adipocytes. 66 59

Local injection of substance P (SP) into the ventral portion of the nucleus gigantocellularis, nucleus reticularis lateralis, and nucleus retrofacialis of the ventrolateral medulla oblongata (VLM) or direct application on the ventral surface of the medulla oblongata caused marked stimulation of tidal volume (VT) and/or minute ventilation (VE). The ventilatory response to hypoxia was significantly blunted after SP in the VLM but not in the dorsal medulla oblongata (DM) (nucleus tractus solitarius). The SP antagonist [D-Pro2,D-Trp7,9]SP almost completely inhibited this response when applied locally to a wide area of the superficial layer of the VLM but not of the DM. Unilateral or bilateral application of 0.3-1.5 nmol of the SP antagonist in the VLM (corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment) markedly attenuated the response to a 5% CO2 inhalation. The inhibition of the CO2 response was seen after [D-Pro2,D-Trp7,9]SP in the rostral areas of the medulla oblongata corresponding to the corpus trapezoideum and the caudal region extending from the rootlets of the nucleus hypoglossus to the first cervical segment of the cervical cord. Electric somatosensory-induced ventilatory stimulation could be depressed by approximately 70% by [D-Pro2,D-Trp7,9]SP locally applied on the surface of the VLM. We conclude that SP is involved in the hypoxic, hypercapnic, and somatosensory ventilatory responses in the rat. However, these respiratory reflexes are mediated via different neuronal pools in the medulla oblongata, mainly the VLM.
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PMID:Substance P in the ventrolateral medulla oblongata regulates ventilatory responses. 169 74

1. Responses of primary sensory neurons to substance P applications by perfusion were studied with intracellular recording techniques in in vitro slice preparations of trigeminal root ganglia (guinea pigs). Application of substance P in micromolar doses produced reversible depolarizations of 2-47 mV in 48 out of 64 neurons. The depolarizing influence facilitated repetitive spike discharge evoked by current-pulse injection. Evidence of desensitization was observed during prolonged or repeated applications of the peptide. 2. The responses to substance P were associated with decreased input resistance, although increased input resistance was observed in neurons where the resting membrane potential was compensated with DC injection. In single-electrode voltage-clamp (SEVC) recordings, substance P evoked an inward shift in the holding current and reduced an outwardly rectifying component in the I-V relationships. The reversal potential for the substance P response could not be determined. These results suggested that the perikaryal response to substance P has a complex ionic mechanism involving activation and deactivation of membrane conductances. 3. Substance P-induced depolarizations were greatly attenuated during perfusion with solutions that were deficient in [Na+] or [Mg2+] and were not significantly affected during perfusion with low-[Ca2+]-, CO2(+)-containing solutions. 4. In the voltage-clamp investigations, an inward current contributed to the substance P responses during combined application with the K(+)-channel blockers, 4-aminopyridine (4-AP) and tetraethylammonium (TEA). This current was not abolished by the inclusion of CsCl in the perfusing solution or by internal Cs+ application from the recording electrode, suggesting that an anomalous inward rectifier was not involved in the responses to substance P.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ionic mechanism of substance P actions on neurons in trigeminal root ganglia. 169 60

We have examined the ability of the endothelium of human epicardial coronary arteries to secrete vasorelaxant substances in response to pharmacological stimulation and under basal conditions. In addition, we have attempted to characterise the chemical identity and biochemical pathway for the synthesis of endothelial derived relaxing factor. Human epicardial coronary arteries were removed from patients who were undergoing heart transplantation for reasons other than ischaemic heart disease. Arteries were cut into segments and suspended in 5 ml organ baths containing a modified Tyrodes solution at 37 degrees C, and gassed with a mixture of 95% oxygen and 5% carbon dioxide. Substance P (10(-10) - 10(-7) M) elicited a dose-dependent relaxation of the coronary segments but this action of substance P was dependent upon an intact endothelium. The maximum response of substance P was equivalent to 89 +/- 8.5% of the maximum effect induced by 1 microgram/ml glyceryl trinitrate. This vasorelaxant effect of substance P was unaffected by the presence of 10(-6) M indomethacin. L-NG-monomethyl-arginine (10(-4) M), a specific inhibitor of formation of nitric oxide from L-arginine, antagonised the relaxations induced by substance P, decreasing the maximum response of substance P to 34 +/- 10.5% of the response to glyceryl trinitrate. Upon application, L-NG-monomethyl-arginine caused a further 23.1 +/- 3.0 increase in tension on preconstricted vessels. This increase in tension was reversed with the addition of L-arginine, but was unaffected by D-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The role of nitric oxide in mediating endothelium dependent relaxations in the human epicardial coronary artery. 170 57

Ventilatory responses to hypoxia and hypercapnia were measured by indirect plethysmography in unanesthetized unrestrained adult rats injected neonatally with capsaicin (50 mg/kg) or vehicle. Such capsaicin treatment ablates a subpopulation of primary afferent fibers containing substance P and various other neuropeptides. Ventilation was measured while the rats breathed air, 12% O2 in N2, 8% O2 in N2, 5% CO2 in O2, or 8% CO2 in O2. Neonatal treatment with capsaicin caused marked alterations in both the magnitude and composition of the hypoxic but not hypercapnic ventilatory response. The increase in minute ventilation evoked by hypoxia in the vehicle-treated rats resulted entirely from an increase in respiratory frequency. In the capsaicin-treated rats the hypoxic ventilatory response was significantly reduced owing to an attenuation of the frequency response. Although both groups responded to hypoxia with a shortening in inspiratory and expiratory times, rats treated with capsaicin displayed less shortening of both respiratory phases. By contrast, hypercapnia induced a brisk ventilatory response in the capsaicin-treated group that was similar in magnitude and pattern to that observed in the vehicle-treated group. Analysis of the components of the hypercapnic ventilatory responses revealed no significant differences between the two groups. We, therefore, conclude that neuropeptide-containing C-fibers are essential for the tachypnic component of the ventilatory response to hypoxia but not hypercapnia.
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PMID:Ventilatory responses to hypoxia and hypercapnia in awake rats pretreated with capsaicin. 170 32

Possible differences in the abilities of esophageal body and lower esophageal sphincter muscles to utilize substrates to support agonist-induced contractions were studied. Strips of longitudinal, circular, and lower esophageal sphincter muscle from the opossum esophagus were first contracted to approximately 70% of the maximal contraction elicited by acetylcholine, histamine, or substance P. The tissues were then exhausted by exposure to 5 x 10(-4) M carbachol and a 15% O2-5% CO2-80% N2 gas mixture for 90 min. They were next reequilibrated with one of a number of alternative substrates and 95% O2-5% CO2 for 3 hr. Responses to the initial agonist doses were again noted and compared to controls. The alternative substrates were: 2-deoxyglucose, glucose, fructose 1-6 diphosphate, pyruvate, lactate, acetate, butyrate, caprylate, histidine, leucine, aspartate, alanine, succinate, acetoacetone, and beta-hydroxybutyrate. The results obtained show qualitative differences in the ability of the three muscle types to use these substrates. More importantly, however, the ability of any one substrate to support contractions was a function of the agonist used to stimulate the muscle. The evidence suggests, therefore, that not all pharmacologic receptors have equal access to intracellular energy sources.
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PMID:Paradoxical relationship between substrates and agonist-induced contractions of opossum esophageal body and sphincter in vitro. 171 20

The isosteric methyleneoxy psi (CH2O) function was employed as a novel peptide-bond surrogate and incorporated into sequences of two neuropeptides, substance P (SP) and enkephalin. A pseudopeptide analogue [pGlu6,Phe8 psi(CH2O)Gly9]SP6-11 (7) of SP related C-terminal hexapeptide [pGlu6]SP6-11 and two pseudopeptide analogues of [Leu5]enkephalinamide, [Tyr1 psi (CH2O)Gly2, Leu5] enkephalinamide (11) and [Gly2 psi (CH2O)-Gly3, Leu5]enkephalinamide (17), were synthesized. The N alpha-protected pseudodipeptidic units were incorporated in the appropriate peptide sequences by using conventional coupling methods in solution. Compound 7 was a potent agonist (EC50 = 4.8 nM) of substance P as compared to the parent peptide [pGlu6]SP6-11 (EC50 = 1.2 nM), in stimulating contraction of the isolated guinea pig ileum (GPI). Analogue 7 was more potent on the neuronal (NK-3) than on the muscular (NK-1) tachykinin receptors in the GPI as shown by the ratio of activities, EC50 (NK-1)/EC50 (NK-3) = 3.16, thus displaying an improved selectivity for the NK-3 tachykinin receptor subtype as compared to that of [pGlu6]SP6-11, EC50 (NK-1)/EC50 (NK-3) = 0.44. In the rat vas deferens (RVD) assay, a typical NK-2 system, the pseudopeptide analogue 7 was (EC50 = 2 microM) 10-fold more potent than the parent peptide and 20-fold less potent than eledoisin, an NK-2 selective tachykinin. The pseudopeptide enkephalin analogue 17 had low biological activity when tested in the electrically induced GPI (EC50 = 2.3 microM) and was inactive in the mouse vas deferens (MVD) assay. In the rat brain membrane (RBM) binding assay analogue 17 had low affinity (in the micromolar range) for both the mu and delta binding sites. In contrast, analogue 11 was a potent enkephalin agonist (EC50 = 30 nM), being equipotent to [D-Ala2, Leu5]enkephalinamide (DALE) in the GPI assay. In the MVD, analogue 11 showed a substantially reduced activity (EC50 = 92 nM), being about 10-fold less potent than DALE. In the RBM binding assay analogue 11 showed high affinity (in the nanomolar range) for both mu and delta binding sites with increased selectivity for the delta sites as shown by the ratio of the apparent affinities for both receptors, Ki (delta)/Ki (mu) = 2.1. The contribution of the modified peptide bonds in the mode of interaction of SP and enkephalin at their corresponding receptors is discussed.
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PMID:Pseudopeptide analogues of substance P and leucine enkephalinamide containing the psi (CH2O) modification: synthesis and biological activity. 171 57

Following the recent discovery of a new substance P (SP) competitive pancreatic acini cell receptor antagonist containing a reduced peptide bond in place of the C-terminal peptide bond, a new series of full chain and short chain (heptapeptide and hexapeptide) substance P analogues have been prepared in which one of the C-terminal-region peptide bonds has been replaced by CH2NH or CH2O groups. They were compared for their ability to recognize NK1 and/or NK2 tachykinin receptor binding sites on guinea pig ileum and rat duodenum smooth muscle preparations, respectively. It was found that all full sequence SP pseudopeptides were agonists with much reduced bioactivity in both tested systems and, in addition, [Gly9 psi(CH2NH)Leu10,Leu11]SP was found to be a relatively selective agonist for NK1 binding sites. Substitution of leucine at position 11 of SP heptapseudopeptides with phenylalanine generated a pseudopeptide with weak agonist activity when Gln at position 5 was replaced by D-Phe, or antagonists when this residue was replaced by D-Nal or D-Cpa. [Leu10 psi(CH2NH)Leu11]SP-(6-11) with Gln at position 6 substituted by D-Phe was a relatively stronger antagonist in both assay systems. These results suggest that, as with several other peptide systems of late, manipulation of the peptide bonds in SP can produce receptor antagonists which in some cases approach the potency of the classic spantide series and, furthermore, that the approach might be used to induce NK receptor specificity in both agonist and antagonist analogs.
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PMID:New reduced peptide bond substance P agonists and antagonists: effects on smooth muscle contraction. 172 44

To investigate the relationship between tachykinins and air ventilation-induced airway constriction after heart ligation, 26 guinea pigs were divided into three groups: Group 1, control (n = 15); Group 2, tachykinin depletion via pretreatment with capsaicin (n = 7); and Group 3, isocapnic ventilation (n = 4). To examine the age effect, the first two groups were further separated into two subgroups: young (n = 12) and mature (n = 10). Animals were anesthetized with pentobarbital, sternotomized and artificially ventilated with room air or with 5% CO2 gas mixture. Before (baseline) and after heart ligation, tidal volume and transpulmonary pressure (Ptp) were recorded during ventilation, and the maximal expiratory flow-volume curve was periodically obtained. Minimal volume (lung volume at Ptp = 0) was determined by neon dilution. Within 30 min after heart ligation in the control group, air ventilation significantly decreased dynamic compliance, vital capacity, peak maximal expiratory flow, maximal expiratory flow at 50% total lung capacity, and forced expiratory volume in 0.2 sec. Tachykinin depletion significantly prevented, whereas isocapnic (5% CO2) ventilation failed to alter, the above changes. Young and mature subgroups showed similar results. Our data indicate that air ventilation after heart ligation induced severe airway constriction and that this bronchoconstriction can be prevented by tachykinin depletion.
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PMID:The role of tachykinins in air ventilation-induced bronchoconstriction in postmortem guinea pigs. 212 Jul 59

The effects of methionine enkephalin (ME) and substance P (SP) were tested on the chemosensory discharge of the cat carotid body-nerve preparation in vitro. ME superfused in concentrations of 10(-8) to 10(-5) M depressed the sensory discharge, an effect followed by receptor excitation (rebound). Bolus applications of ME (30 ng to 3.0 microgram) induced variable effects (excitation or depression) on the discharge, excitation being more pronounced with the smaller doses. Superfusions with SP (10(-8) to 10(-5) M) either excited or depressed the discharge, excitation being more pronounced with higher SP concentrations (i.e. 10(-6) M). Bolus applications of SP (43 ng to 0.5 micrograms) also excited or depressed the sensory discharge. These variations may be dose-dependent. Superfused ME (10(-6) M) significantly depressed the chemoreceptor response to hypoxia (100% N2) and hypercapnia (6% CO2, pH 7.43). The responses to NaCN and acidity (pH 6.0) were marginally depressed. Superfused SP (10(-6) M) clearly depressed the responses to hypoxia, those to hypercapnia and NaCN were marginally affected but the effects of acidity were not altered. When the peptides were tested against the receptor responses to exogenously applied putative neurotransmitters (ACh, dopamine--DA), it was found that ME tended to depress both the ACh and DA actions whereas SP (10(-6) M) tended to increase their effects. Superfusions with naloxone (10(-6) M) increased the basal chemosensory discharge and this enkephalin blocker partially relieved the depressant effect of ME on the ACh-induced response. It is concluded that carotid body chemoreceptors have excitatory and inhibitory reactive sites to both ME and SP although their precise location is still unknown.
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PMID:Effects of methionine-enkephalin and substance P on the chemosensory discharge of the cat carotid body. 241 43


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