Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isometric tension developed by rat soleus and extensor digitorum longus (EDL) muscles in response to acetylcholine (Ach) applied in vitro was recorded. Tension of contractures elicited in response to Ach increased after muscles had been incubated with phospholipase C, pepsin, or soluble fractions prepared from muscle homogenate. Using intracellular microelectrodes, resting membrane potential (RMP) and depolarisation in response to Ach added to the bathing medium were recorded in endplate-free regions of the muscle fibres. No significant change in RMP was observed in muscles incubated with soluble muscle fraction or phospholipase C, but depolarisation in response to Ach or carbachol was significantly increased. The time course for the increase in depolarisation and the contracture response to Ach was similar. When all available receptors were blocked with alpha-bungarotoxin prior to incubation so that no response to Ach could be elicited, with subsequent incubation in muscle soluble fraction or phospholipase C, both contractures and depolarisation in response to Ach returned. These results support the hypothesis that receptors, not previously available to interact with Ach or alpha-bungarotoxin were revealed following incubation.
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PMID:The effect of hydrolytic enzymes on the acetylcholine sensitivity of the skeletal muscle cell membrane. 36 54

Rabbit ileum strips were functionally skinned by exposure to staphylococcal alpha-toxin. Incubation of the strips in the ATP analog ATP gamma S or [35S]ATP gamma S in the presence of Ca2+ (but not in the absence of Ca2+) resulted in a maximal Ca2+-insensitive activated tension that persisted following removal of Ca2+. Correlated with this tension was 35S-labeling of the 20,000-dalton myosin light chain, LC20, that persisted even after removal of Ca2+. Tension in these strips partially relaxed when exposed to ATP (alpha,beta-methylene). In contrast, alpha-toxin-treated strips exposed to ATP or [gamma-32P]ATP showed Ca2+-sensitive, reversible activated tension and reversible 32P-labeling of the LC20. These results are consistent with a currently proposed model of Ca2+ control of smooth muscle contraction involving a myosin light chain kinase-phosphatase system.
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PMID:Irreversible thiophosphorylation and activation of tension in functionally skinned rabbit ileum strips by [35S]ATP gamma S. 50 Jun 32

1. Strips of smooth muscle from rat anococcygeus and guinea-pig portal vein were treated with solutions containing crude alpha-toxin from the bacterium Staphylococcus aureus. This rendered the surface membrane permeable to small molecular weight substances, but left functional sarcolemmal adrenoceptors. Tension measurements from these preparations were used to investigate the effects of guanosine-5'-triphosphate (GTP) on the noradrenaline-induced Ca2+ release from the sarcoplasmic reticulum (SR) of the smooth muscle of rat anococcygeus and guinea-pig portal vein. 2. Under conditions of low Ca2+ buffering (0.2 mM-EGTA), applying a maximal dose of noradrenaline (30 microM) to a toxin-permeabilized strip of anococcygeus muscle and longitudinal muscle of guinea-pig portal vein caused a transient contracture. Subsequent exposures to noradrenaline resulted in progressively smaller contractures. However, the rate of decline in the size of the noradrenaline-induced contracture was greater in rat anococcygeus muscle than in guinea-pig portal vein preparations. The decline in the size of the contracture in toxin-permeabilized anococcygeus muscle was not due to a fall in the Ca2+ content of the SR or a reduced Ca2+ release from the SR in response to myo-inositol 1,4,5-trisphosphate (IP3). 3. The tension transients due to noradrenaline were enhanced and maintained in the presence of 100 microM-GTP in toxin-permeabilized guinea-pig portal vein. Addition of 100 microM-GTP caused a transient contracture in permeabilized rat anococcygeus muscle and only promoted the next noradrenaline response, thereafter the amplitude of the contractures decayed to zero. 4. Addition of guanosine-5'-O-(2 thiodiphosphate) (GDP-beta-S, 100 microM) would be expected to cause a reversible reduction of the noradrenaline response by binding to the intermediary G-protein. This was observed in toxin-permeabilized portal vein, but in rat anococcygeus muscle, GDP-beta-S caused slowing of the response to noradrenaline, thereafter the response to noradrenaline was absent. The noradrenaline response did not recover when GDP-beta-S was removed. 5. The non-metabolizable form of GTP, guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S, 100 microM), caused a transient contracture in both toxin-permeabilized rat anococcygeus muscle and guinea-pig portal vein. In both these tissues, the addition of GTP-gamma-S resulted in the irreversible inhibition of the response to noradrenaline. 6. In the presence of a high concentration (10 mM) of the Ca2+ buffer EGTA, GTP (100 microM) and noradrenaline (30 microM) increased Ca(2+)-activated force in both tissues.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:GTP and noradrenaline-induced force in isolated toxin-permeabilized rat anococcygeus and guinea-pig portal vein. 189 Jun 48

It has previously been shown that human umbilical artery (HUA) smooth muscle produces thromboxane A2 in response to increasing oxygen levels and that this thromboxane promotes contraction. To investigate the intracellular action of thromboxane A2, strips of HUA longitudinal smooth muscle were permeabilized using alpha-toxin from the bacterium Staphylococcus aureus. This treatment rendered the surface membrane permeable to low-molecular-weight substances but left functional thromboxane A2 receptors. Tension measurements were used to investigate the effect of the stable thromboxane A2 analogue, U-46619, on the Ca2+ sensitivity of smooth muscle contractile proteins. U-46619 (1 nM to 1 microM) potentiated submaximal Ca(2+)-activated force (generated by [Ca2+], 50 nM to 3 microM) but not maximal Ca(2+)-activated force (generated by [Ca2+], 10-100 microM). The specific thromboxane A2 receptor antagonist, GR-32191B (1 microM), inhibited the action of U-46619 (0.1 microM). The potentiation of submaximal Ca(2+)-activated force produced by the muscle in response to U-46619 (0.1 microM) was antagonized by guanosine 5'-O-(2-thiodiphosphate) (1 mM), the nonhydrolyzable analogue of GDP, and mimicked by guanosine 5'-O-(3-thiotriphosphate) (100 microM), the nonhydrolyzable analogue of GTP. These results suggest that U-46619 acts via the previously identified thromboxane A2 receptor to promote Ca2+ sensitivity of tension production in HUA smooth muscle. Furthermore, this effect appears to be mediated via a G protein.
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PMID:Thromboxane A2 analogue, U-46619, potentiates calcium-activated force in human umbilical artery. 832 17

We investigated the signaling pathways modulating histamine- and prostaglandin F2 alpha (PGF2 alpha)-induced contractions of human chorionic vasculature. Neomycin, a phospholipase C (PLC) inhibitor, attenuated PGF2 alpha and histamine contractile responses 40 and 60%, respectively. AIF4-, a G protein stimulant, induced a strong contraction alone but blocked histamine- and PGF2 alpha-induced contractions. Staurosporine (100 nM), a protein kinase C (PKC) inhibitor, attenuated the PGF2 alpha-dependent contractions by 50% but did not affect the histamine response. However, higher nonspecific inhibitory concentrations of staurosporine (1-2 microM) abolished histamine and PGF2 alpha contractile responses, presumably by inhibiting other protein kinases. Although, the PKC phorbol 12-myristate 13-acetate (PMA) did not affect basal tension or PGF2 alpha-dependent contractions, the histamine response was attenuated by 30%. Sodium nitroprusside (SNP), a guanylyl cyclase stimulant, strongly attenuated histamine- and PGF2 alpha-induced contractions. Tension increases were similarly attenuated by forskolin and isobutylmethylxanthine (IBMX), which increase intracellular cyclic AMP. In vessel rings prelabeled with [3H]myoinositol, PGF2 alpha and histamine increased [3H]inositol phosphate (IP) production 400 and 100%, respectively, indicating that PLC is stimulated by both agonists. Neomycin inhibited histamine- and PGF2 alpha-induced increases in [3H]IP production 60 and 40%, respectively. Staurosporine (0.1-1 microM) and PMA did not affect histamine- or PGF2 alpha-stimulated IP production. AIF4-alone increased IP production but blocked histamine- and PGF(2 alpha)-dependent IP increases. These observations suggest that at least part of the contractile responses due to PGF2 alpha and histamine are associated with stimulation of PLC through an AIF4(-)-sensitive G protein. The role of PKC is variable, because PGF2 alpha but not histamine tension responses were attenuated by PKC inhibition. In addition, therapeutic agents that increase cyclic AMP and cyclic GMP attenuated histamine- and PGF2 alpha-induced contractions in human chorionic vasculature, although histamine responses were relatively more sensitive to these agents.
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PMID:Mechanisms of prostaglandin F2 alpha and histamine-induced contractions in human chorionic vasculature. 887 81

The sensitivity of the myofilaments to Ca2+ is increased during agonist-induced contraction of vascular smooth muscle. Given the important contribution of vascular tone to the elevation of peripheral resistance observed in genetic hypertension, we have investigated whether alterations in myofilament Ca2+ sensitivity occur in small arteries from spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto (WKY) controls during the developmental and established phases of hypertension. Segments of mesenteric, renal, and femoral artery with an average lumen diameter <300 microm from 5- or 20-week-old rats were mounted in a wire myograph. Morphological measurements were made and the vessels permeabilized with Staphylococcus aureus alpha-toxin. Dose-response curves to increasing concentrations of Ca2+ were obtained and the ability of 100 nmol/L endothelin-1 (ET-1) or 10 micromol/L norepinephrine (NE) in the presence of 10 micromol/L GTP to enhance tension in response to low Ca2+ (pCa6.7) was determined. Systolic, diastolic, and mean blood pressures were higher in SHR than in WKY at 5 and 20 weeks. The media thickness:lumen diameter ratio was increased in mesenteric and femoral arteries from SHR compared with WKY at 5 and 20 weeks. There was no difference in media thickness:lumen diameter ratio in renal arteries or between 5- and 20-week animals in any vascular bed. The pCa curves were not different in mesenteric, renal, or femoral arteries from hypertensive compared with normotensive rats or between age groups, except in femoral arteries at 20 weeks, which exhibited a greater sensitivity to Ca2+ in SHR. Tension developed in response to maximal Ca2+ (pCa5.0) was greater in permeabilized mesenteric arteries from SHR compared with WKY at 20 weeks of age only; media stress was again similar in both strains but increased in older animals compared with younger animals in mesenteric arteries from WKY. The submaximal contraction induced by pCa6.7 was greater in femoral and renal than mesenteric arteries. GTP (10 micromol/L) augmented the tension developed to pCa6.7 in mesenteric arteries at 5 and 20 weeks and in renal arteries at 20 weeks. Addition of 100 nmol/L ET-1 or 10 micromol/L NE in the continued presence of GTP markedly increased tension in mesenteric arteries at 5 and 20 weeks. In renal arteries, 10 micromol/L NE enhanced Ca2+ sensitivity in the presence of GTP in SHR at 5 and 20 weeks and WKY at 5 weeks. In femoral arteries, there was a tendency for ET-1 and NE to increase Ca2+ sensitivity, but this increase was significant in WKY at 20 weeks (ET-1) and SHR at 5 weeks (NE) only. We have demonstrated that the sensitivity of the myofilaments to Ca2+ and ET-1- or NE-induced Ca2+ sensitization is not different in permeabilized small mesenteric, renal, or femoral arteries from SHR compared with WKY controls. Only in SHR mesenteric arteries at 20 weeks of age was there evidence of increased active tension in response to maximal Ca2+, despite structural differences, consistent with increased muscle mass in femoral arteries from SHR. We conclude that it is unlikely that a ubiquitous abnormality of the sensitivity of the contractile apparatus to Ca2+ or agonist-induced Ca2+ sensitization in vascular smooth muscle underlies the elevated total peripheral resistance associated with hypertension.
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PMID:Calcium sensitivity and agonist-induced calcium sensitization in small arteries of young and adult spontaneously hypertensive rats. 931 30