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)

To investigate whether ATP-sensitive K+ channels exist in gastric smooth muscle of the guinea pig and whether they are modulated by substance P, we recorded lemakalim-activated K+ currents from freshly isolated cells using the standard whole-cell configuration. With 0.1 mM ATP and 140 mM K+ in the pipette and 90 mM K+ in the bath solution and a holding potential of -80 mV, lemakalim (10 microM) activated a glibenclamide-sensitive inward current with a mean amplitude of -224+/-34 pA. These currents were voltage-independent from -90 to 0 mV and K+-selective. Increasing the intracellular ATP concentrations from 0.1 to 3 mM reduced the lemakalim-activated currents by about five-fold. External barium and cesium inhibited the lemakalim-activated currents in a dose-dependent manner. External tetraethylammonium (10 mM) inhibited the lemakalim-activated currents by 66+/-15%. Bath application of substance P (5 microM) inhibited the lemakalim-activated currents by 53+/-13% and this inhibition was absent when 0.5 mM guanosine 5'-O-(2-thiodiphosphate) (GDPbetaS) was in the pipette. Phorbol 12,13-dibutyrate (PDB) inhibited the lemakalim-activated currents by 71+/-3%. Chelerythrine (1 microM) reduced the substance P-induced inhibition of lemakalim-activated currents by 22.2+/-11.3%. These results suggest the presence of ATP-sensitive K+ channels in gastric smooth muscle and that substance P inhibits ATP-sensitive K+ channels via G-protein through protein kinase C activation.
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PMID:ATP-sensitive K+ current and its modulation by substance P in gastric myocytes isolated from guinea pig. 980 72

1. Magnesium (Mg)-deficient rats develop a mechanical hyperalgesia which is reversed by a N-Methyl-D-Aspartate (NMDA) receptor antagonist. Given that functioning of this receptor-channel is modulated by Mg, we wondered whether facilitated activation of NMDA receptors in Mg deficiency state may in turn trigger a cascade of specific intracellular events present in persistent pain. Hence, we tested several antagonists of NMDA and non-NMDA receptors as well as compounds interfering with the functioning of intracellular second messengers for effects on hyperalgesia in Mg-deficient rats. 2. Hyperalgesic Mg-deficient rats were administered intrathecally (10 microl) or intraperitoneally with different antagonists. After drug injection, pain sensitivity was evaluated by assessing the vocalization threshold in response to a mechanical stimulus (paw pressure test) over 2 h. 3. Intrathecal administration of MgSO4 (1.6, 3.2, 4.8, 6.6 micromol) as well as NMDA receptor antagonists such as MK-801 (0.6, 6.0, 60 nmol), AP-5 (10.2, 40.6, 162.3 nmol) and DCKA (0.97, 9.7, 97 nmol) dose-dependently reversed the hyperalgesia. Chelerythrine chloride, a protein kinase C (PKC) inhibitor (1, 10.4, 104.2 nmol) and 7-NI, a specific nitric oxide (NO) synthase inhibitor (37.5, 75, 150 micromol x kg(-1), i.p.) induced an anti-hyperalgesic effect in a dose-dependent manner. SR-140333 (0.15, 1.5, 15 nmol) and SR-48968 (0.17, 1.7, 17 nmol), antagonists of neurokinin receptors, produced a significant, but moderate, increase in vocalization threshold. 4. These results demonstrate that Mg-deficiency induces a sensitization of nociceptive pathways in the spinal cord which involves NMDA and non-NMDA receptors. Furthermore, the data is consistent with an active role of PKC, NO and, to a lesser extent substance P in the intracellular mechanisms leading to hyperalgesia.
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PMID:Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats. 1170 42

Endothelin 1 (ET-1) and its receptors, ETA and ETB, play important roles in regulating renal function and blood pressure, and these components are expressed in sensory nerves. Activation of transient receptor potential vanilloid (TRPV) 1 channels expressed in sensory nerves innervating the renal pelvis enhances afferent renal nerve activity (ARNA), diuresis, and natriuresis. We tested the hypothesis that ET-1 increases ARNA via activation of ETB, whereas ETA counterbalances ETB in wild-type (WT) but not TRPV1-null mutant mice. ET-1 alone or with BQ123, an ETA antagonist, perfused into the left renal pelvis increased ipsilateral ARNA in WT but not in TRPV1-null mutant mice, and ARNA increases were greater in the latter. [Ala1, 3,11,15]-endothelin 1, an ETB agonist, increased ARNA that was greater than that induced by ET-1 in WT mice only. [Ala1, 3,11,15]-endothelin 1-induced increases in ARNA were abolished by chelerythrine, a protein kinase C inhibitor, but not by H89, a protein kinase A inhibitor. Chelerythrine, H89, and BQ788, an ETB antagonist, did not affect ARNA triggered by capsaicin in WT mice. Substance P release from the renal pelvis was increased by [Ala1, 3,11,15]-endothelin 1 in WT mice only, and the increase was abolished by chelerythrine but not by H89. Chelerythrine, H89, and BQ788 did not affect capsaicin-induced substance P release. Our data show that ET1 increases ARNA via activation of ETB, whereas ETA counterbalances ETB in WT but not in TRPV1-null mutant mice, suggesting that TRPV1 mediates ETB-dependent increases in ARNA, diuresis, and natriuresis possibly via the protein kinase C pathway.
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PMID:Ablation of transient receptor potential vanilloid 1 abolishes endothelin-induced increases in afferent renal nerve activity: mechanisms and functional significance. 1985 8