Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the undecapeptide, substance P(SP), on the secretion of mucin and proteolytic enzymes from dispersed cells of the rat submandibular gland were studied. The peptide, at a concentration of 1 X 10(-7) M, stimulated the release of 31.9 +/- 3.0% (mean +/- SEM) of intracellular mucin over 40 min, compared with 12.5 +/- 1.5% in untreated controls (p less than 0.01). This effect was duplicated by the homologous peptides, physalaemin, and eledoisin-related peptide. Substance P action was not affected by pre-incubation of cells with phentolamine or propranolol and was therefore independent of adrenergic stimulation. Furthermore, SP did not enhance the intracellular concentrations of cyclic AMP or cyclic GMP, confirming that cyclic nucleotides were not involved in its stimulus-secretion coupling mechanism. The isoproterenol-stimulated secretion of mucin from dispersed cells was reduced to 75.7% of the normal response (p less than 0.01) after a brief exposure to SP. This inhibitory effect was probably mediated by intracellular events rather than by direct effects on cell surface receptors. However, mucin release after treatment with SP followed by norepinephrine (NE) was 161% of that caused by NE alone (p less than 0.01) and may reflect an additive response to the independent stimulation of SP and NE receptors. Substance P and related peptides had no effect on arginine esterase secretion in the experimental model, although a response was elicited by alpha- and beta-adrenergic agonists. It is, therefore, proposed that serous cells of the granular convoluted tubule in the rat submandibular gland lack substance P receptors.
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PMID:Effect of substance P on exocrine secretion by rat submandibular gland cells. 620 29

When retinal sections were isolated from dark-adapted bullfrogs and placed in normal ringer's solution, they contained 40.7 +/- 0.2 pmol cGMP/mg protein (mean +/- SEM, 30 samples). When isolated, dark-adapted retinal sections were removed from normal ringer's solution and placed in calcium-deficient ringer's solution with 3 mM EGTA, there was about a threefold rise in cyclic GMP (cGMP) levels by 1.5 min and about a 10-fold rise by 5 min. The cGMP level remained high with no detectable decrease for at least 40 min (the longest time measured). When isolated, dark- adapted retinal sections were removed from normal ringer's solution and placed in ringer's solution which contained high- calcium (20 mM CaCl(2)), there was a slow but significant decrease in cGMP levels. After 20 min in high-calcium ringer's solution the cGMP level was 0.58 +/- 0.07 (mean +/- SEM, eight samples) of the cGMP level in normal ringer's solution incubated for the same time. The rate at which 10-fold elevated cGMP levels in low calcium decreased upon illumination was examined using quick-freezing techniques on the retinal sections. The elevated cGMP level in retinal sections incubated in low-calcium decreased upon illumination was examined using quick-freezing techniques on the retinal sections. The elevated cGMP level in retinal sections incubated in low-calcium ringer's solution was found to decay about 15-fold faster than cGMP levels in retinal sections incubated in normal ringer's solution. The CGMP level in low calcium was significantly different (P=0.005) after 1 s illumination, whereas the cGMP level in normal calcium was not significantly different.
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PMID:Calcium effects on frog retinal cyclic guanosine 3', 5'-monophosphate levels and their light-initiated rate of decay. 624 21

Six normotensive volunteers were infused with L-adrenaline at 0.01, 0.03, 0.05, 0.075 and 0.10 microgram/kg-1 min-1, each increment lasted 10 min. Plasma adrenaline rose from 0.27 to 4.61 nmol/l, and there were dose-related increases in plasma renin activity, blood glucose, plasma cyclic AMP and plasma free fatty acids, but not in plasma noradrenaline and cyclic GMP. Levels of circulating adrenaline previously noted in essential hypertensives had minimal cardiovascular effects. The secretion rate of adrenaline and its rate of clearance from the circulation were calculated from plasma samples taken during an hour-long infusion (0.083 +/- 0.006 microgram kg-1 min-1) of L-adrenaline in the same individuals. The secretion rate ranged from 1.40 to 6.01 nmol/min with a mean (+/- SEM, 6) of 2.82 +/- 0.76 nmol/min. Mean clearance (+/- SEM, 6) was 9.41 +/- 1.37 l/min and ranged from 4.86 to 14.61 l/min. The decline of plasma adrenaline following the infusion was biexponential. Plasma adrenaline is unlikely to be of primary importance in the elevation of blood pressure, either directly, via renin release or by noradrenaline release via presynaptic beta receptors. However, variation in clearance between subjects limits the use of plasma levels as an interindividual index of adrenal release of adrenaline. The relationship between sympathoadrenal activity and plasma adrenaline may be further perturbed by equilibration between the circulation and sites of tissue uptake. The lower levels of plasma adrenaline than of noradrenaline appear to result from both a slower rate of secretion and a higher rate of clearance from the circulation.
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PMID:Circulating adrenaline and blood pressure: the metabolic effects and kinetics of infused adrenaline in man. 677 75

Although it has been proposed that the circulating granulocyte (PMN) is an effector cell that causes pulmonary vascular injury in the adult respiratory distress syndrome (ARDS), the functional status of PMNs from patients with this disorder has not been previously defined. In the present study we found that PMNs in samples of pulmonary artery blood from patients with ARDS are in a functionally and metabolically activated state. The mean chemotactic index of PMNs from ARDS patients was 172 +/- 22 SEM compared with a mean chemotactic index of 79 +/- 8 of PMNs from normal subjects (p = 0.0001), a 227 +/- 24% increase over the control value. Respiratory burst activity of PMNs, as assessed by the chemiluminescence response (CL), was 151 +/- 12% of control (mean peak CL of PMNs from patients with ARDS, 166 +/- 31 cpm X 10(3); mean peak CL of normal PMNs, 105 +/- 16 cpm X 10(3); p = 0.04), suggesting that granulocytes from patients with ARDS are likely to generate increased quantities of active oxygen metabolites when stimulated. The chemotactic and chemiluminescence responses of PMNs from patients with ARDS were much greater than those of critically ill patients without ARDS, were enhanced in the absence of concurrent bacterial infection, and did not appear to be blunted by recent administration of glucocorticoids. The PMNs from patients with ARDS had increased ratios of intracellular cyclic GMP to cyclic AMP (165 +/- 5% of control, p = 0.0002), which may be related to the enhanced metabolic activity. Release of superoxide anion, a potential mediator of endothelial injury, was increased over that of control by PMNs from 4 of 8 patients with ARDS (mean, 205 +/- 71% of normal). The results suggest that the circulating PMN is in an activated state in patients with ARDS and may be more likely to release active oxygen species and other inflammatory mediators when perturbed, potentially contributing to pulmonary vascular injury and alveolitis.
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PMID:Functional and metabolic activity of granulocytes from patients with adult respiratory distress syndrome. Evidence for activated neutrophils in the pulmonary circulation. 683 52

In fasting human serum, cholecystokinin (CCK) is not the principal substance which causes in vitro rabbit gallbladder contraction. Removal of CCK by affinity chromatography from fasting sera from 8 healthy adults reduced bioactivity only by 18 +/- 4% (SEM). Unlike CCK, the bioactivity of serum was enhanced by 30 to 57% rather than destroyed by pronase and chymotrypsin respectively and was not inhibited by dibutyryl cGMP. Reduction of serum bioactivity by carboxypeptidase Y indicated that the bioactive substances in serum are peptides. On Sephadex G-50, bioactive substances eluted in positions different from any known form of CCK. Thus, the principal substances in fasting human serum causing in vitro gallbladder contraction are not CCK but are most likely small peptides which act at receptors different from the receptors for CCK.
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PMID:Noncholecystokinin peptides in human serum which cause gallbladder contraction. 716 64

The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8Br-cGMP), a membrane-permeant activator of protein kinase G (PKG), were studied on rat and human connexin43 (Cx43), the most abundant gap junction protein in mammalian heart, which were exogenously expressed in SKHep1 cells. Under dual whole-cell voltage-clamp conditions, 8Br-cGMP decreased gap junctional conductance (gj) in rat Cx43-transfected cells by 24.0 +/- 3.7% (mean +/- SEM, n = 5), whereas gj was not affected in human Cx43-transfected cells by the same treatment. The relaxation of gj in response to steps in transjunctional voltage observed in rat Cx43 transfectants was best fitted with three exponentials. Time constants and amplitudes of the decay phases changed in the presence of 8Br-cGMP. Single rat and human Cx43 gap junction channels were resolved in the presence of halothane. Under control conditions, three single-channel conductance states (gammaj) of about 20, 40-45 and 70 pS were detected, the events of the intermediate size being most frequently observed. In the presence of 8Br-cGMP, the gammaj distribution shifted to the lower size in rat Cx43 but not in human Cx43 transfectants. Immunoblot analyses of Cx43 in subconfluent cultures of rat Cx43 or human Cx43 transfectants showed that 8Br-cGMP did not induce changes in the electrophoretic mobility of Cx43 in either species. However, the basal incorporation of [32P] into rat Cx43 was significantly altered by 8Br-cGMP, whereas this incorporation of [32P] into human Cx43 was not affected. We conclude that 8Br-cGMP modulates phosphorylation of rat Cx43 in SKHep1 cells, but not of human Cx43. This cGMP-dependent phosphorylation of rat Cx43 is associated with a decreased gj, which results from both an increase in the relative frequency of the lowest conductance state and a change in the kinetics of these channels.
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PMID:Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels. 747 32

Atrial natriuretic factor (ANF) reduces the volume of atrial myocytes by inhibiting Na+/K+/2Cl- cotransport. We determined the role of cGMP and cAMP in ANF-induced shrinkage by using digital video microscopy to measure cell volume; volumes are reported relative to control. ANF (1 mumol/L) reversibly reduced atrial cell volume from 1.0 to 0.915 +/- 0.005 (mean +/- SEM). This effect was mimicked by 10 mumol/L 8-bromo-cGMP (8-Br-cGMP), which decreased myocyte volume to 0.894 +/- 0.007 with an ED50 of 0.99 +/- 0.05 mumol/L. In contrast, 100 mumol/L 8-bromo-cAMP (8-Br-cAMP) did not affect volume, and activating the cAMP pathway with 100 mumol/L 8-Br-cAMP did not alter the volume decrease caused by 8-Br-cGMP or ANF. Inhibition of Na+/K+/2Cl- cotransport with bumetanide (1 mumol/L) also reduced cell volume and prevented further shrinkage on subsequent exposure to 8-Br-cGMP. Similarly, 8-Br-cGMP (10 mumol/L) prevented further shrinkage by ANF. Block of Na(+)-H+ exchange, a participant in volume regulation in other cells, did not alter the response to 8-Br-cGMP. More evidence implicating cGMP was obtained by altering its metabolism. LY83583 (10 mumol/L), a guanylate cyclase inhibitor, blocked ANF-induced cell shrinkage. Zaprinast (100 mumol/L), a cGMP-specific phosphodiesterase inhibitor, markedly potentiated the effect of a threshold concentration of ANF (0.01 mumol/L). The actions of ANF, LY83583, and zaprinast on cGMP levels were verified by radioimmunoassay. These data strongly support the idea that the cGMP cascade is the intracellular signaling pathway responsible for ANF-induced atrial cell shrinkage.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:cGMP and atrial natriuretic factor regulate cell volume of rabbit atrial myocytes. 755 21

The possibility that pituitary adenylyl cyclase-activating peptide (PACAP) is an inhibitory neurotransmitter has been investigated in the taenia of the guinea-pig caecum. The action of PACAP on muscle contractility and its ability to alter levels of adenosine-3':5'-cyclic monophosphate (cyclic AMP) and guanosine-3':5'-cyclic monophosphate (cyclic GMP) were investigated. PACAP-1-27 was an effective agonist, giving relaxations comparable in magnitude to isoproterenol; its EC50 was 3.4 x 10(-7) M. PACAP (10(-6) M) caused an almost two-fold increase in cyclic AMP levels; but the level of cyclic GMP was not affected. The relaxation caused by PACAP was slow in onset, with a latency of 5.8 +/- 0.8 s and reached a maximum at 9.1 +/- 1.1 s after onset. The relaxation was significantly reduced by apamin (10(-6) M) and suramin (10(-4) M) but was not reduced by tetrodotoxin (10(-7) M). Relaxation of the taenia coli caused by electrical stimulation of the inhibitory nerves was greatly reduced by apamin but only slightly reduced by suramin. PACAP-like immunoreactivity (-IR) was localised immunohistochemically in varicose nerve fibres within the taenia coli and in the underlying myenteric plexus and circular muscle. Approx. 50% of vasoactive intestinal peptide (VIP)-IR nerve fibres in the taenia also had immunoreactivity for PACAP; conversely, almost all PACAP-IR fibres were immunoreactive for VIP. PACAP-IR and substance P (SP)-IR were generally in separate fibres; only about 5% of SP-IR fibres were PACAP-IR. Radioimmunoassay revealed tissue concentrations of PACAP-1-27 and PACAP-1-38 of 1.0 +/- 0.1 and 2.1 +/- 0.3 (SEM) pmol/g wet weight of tissue, respectively. Material with PACAP-1-27 immunoreactivity co-eluted with authentic PACAP-1-27 on gel filtration chromatography, and PACAP-1-38 immunoreactivity also co-eluted with the authentic peptide. This study provides structural, chemical and pharmacological evidence that PACAP could be involved in inhibitory neurotransmission to the taenia coli of the guinea-pig caecum.
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PMID:Histochemical, pharmacological, biochemical and chromatographic evidence that pituitary adenylyl cyclase activating peptide is involved in inhibitory neurotransmission in the taenia of the guinea-pig caecum. 771 25

We examined renal sodium handling in rats with Hymann nephritis (HEN), an immunologically mediated model of nephrotic syndrome. Rats were studied 9-14 days following i.p. injection of anti-Fx1A antiserum. We previously demonstrated that HEN had a blunted volume expansion natriuresis (2% body weight isotonic saline infused over 5 min), excreting sodium at only half the rate of normal controls (CTL) despite similar increase in plasma atrial natriuretic peptide (ANP) concentration. Urinary excretion of cGMP accumulation by isolate glomeruli and inner medullary collecting duct (IMCD) cells in response to increasing concentration of ANP, and RNP (also called urodilatin). Results (fmol/mg prot/10 min) are means +/- SEM: [table: see text]. Basal accumulation of cGMP was not different among the groups, HEN rats hd reduced cGMP accumulation in response to ANP, and RNP. In binding studies using 125I-ANP, no difference in either density or affinity was found between CTL and HEN rats. Thus, there is a renal resistance to ANP in rats with HEN, which can be extended to other agents acting through the cGMP pathway. This resistance is not due to impaired binding of ANP, but to impaired accumulation of cGMP in responsive tissues, reflecting perhaps increased cGMP catabolism by phosphodiesterase. Such an observation may account for the altered sodium handling in nephrotic rats.
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PMID:[Resistance to the action of atrial natriuretic peptide and urodilatin in Heymann nephritis in vitro]. 775 73

The interactions of the systemic adaptations during and after rapid ventricular pacing, a model of heart failure, were assessed in conscious, unstressed dogs. One week of ventricular tachycardia (260 beats/min) significantly reduced mean +/- SEM cardiac output (2.3 +/- 0.1 to 1.2 +/- 0.1 liter/min), mean arterial pressure (119 +/- 3 to 93 +/- 3 mm Hg), renal blood flow (168 +/- 19 to 96 +/- 9 ml/min), sodium excretion (36 +/- 5 to 10 +/- 4 mEq/d), increased left and right atrial pressures (8 +/- 1 to 21 +/- 1 and 4 +/- 0 to 11 +/- 1 mm Hg, respectively), plasma atrial natriuretic peptide concentration (24 +/- 4 to 141 +/- 38 fmol/ml), plasma cyclic GMP concentration (9 +/- 1 to 16 +/- 4 pmol/ml), and urinary cyclic GMP excretion (0.77 +/- 0.05 to 2.18 +/- 0.34 nmol/min). These changes persisted throughout 3 weeks of pacing. Gradual increases in systemic and renal vascular resistances (to 122 +/- 17 and 1.30 +/- 0.22 mm Hg/liter/min, respectively) and reductions in glomerular filtration rate (65 +/- 6 to 44 +/- 4 ml/min) reached significance during the third week. Resumption of sinus rhythm stimulated a brisk natriuresis and a return of cardiac output, systemic vascular resistance, and hormone concentrations to control values within 7 days. However, increases of left and right atrial pressures (14 +/- 2 and 8 +/- 1 mm Hg, respectively) were still present after 2 months of recovery. In conclusion, persistent increases in cardiac filling pressures were induced by rapid ventricular pacing in conscious, unstressed dogs, whereas the systemic hemodynamic, renal, and hormonal responses were largely reversible during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic, renal, and hormonal effects of rapid ventricular pacing in conscious dogs. 784 52


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