Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. We studied the non-adrenergic, non-cholinergic (NANC) nerve-mediated relaxation induced by electrical stimulation in pig isolated lower urinary tract smooth muscle, and the possible involvement of the L-arginine (L-ARG)/nitric oxide (NO) pathway in this response. 2. Trigonal strips, precontracted by noradrenaline (NA), carbachol or endothelin-1 (ET-1), relaxed frequency-dependently in response to electrical stimulation. Maximum relaxation was obtained at 6-8 Hz, and amounted to 56 +/- 2%, 77 +/- 3% and 62 +/- 6% of the agonist-induced tension in preparations contracted by NA, carbachol, or ET-1, respectively. Exposure to NG-nitro-L-arginine (L-NOARG; 10(-7)-10(-5) M) concentration-dependently reduced the relaxant response in preparations contracted by NA. L-NOARG (10(-6) M) reduced the maximal response to 51 +/- 8% of control. L-NOARG (10(-5) M) abolished all relaxation, and unmasked a contractile component; D-NOARG had no effect. Also in trigonal preparations, where the tension had been raised by carbachol or ET-1, L-NOARG (10(-5) M) markedly reduced relaxations evoked by electrical stimulation. 3. In trigonal preparations contracted by NA, maximal relaxation was increased after pretreatment with L-ARG (10(-3) M), and the inhibitory effect of L-NOARG (10(-6) M) was prevented. Incubation of the trigonal strips with methylene blue had no effect on relaxations elicited at frequencies less than 6 Hz, but a small inhibition was observed at higher frequencies. 4. Administration of NO (present in acidified solution of NaNO2) induced concentration-dependent relaxations in trigonal preparations contracted by NA, carbachol, or ET-1.L-NOARG (10-5 M) and L-ARG (10-3M) had no effect on these relaxations. However, methylene blue (10-S M) significantly shifted the concentration-response curve for NO to the right. NANC-relaxation and NO-induced relaxation of trigonal preparations were both inhibited by oxyhaemoglobin (10-5 M) and pyrogallol (10-4 M).5. In urethral preparations precontracted by NA, electrical stimulation caused frequency-dependent relaxations. A maximum relaxation of 73 +/- 4% was obtained at 10 Hz. Also in the urethra, NANCrelaxation was blocked by L-NOARG (10-5 M), and a contractile response generally appeared.6. Detrusor strips treated with alpha-beta methylene ATP (10-i M) and atropine (10-6 M), and then contracted by ET-1, showed relaxations (19 +/- 3% of the induced tension) in response to electrical field stimulation (2-20 Hz) only when the tension was high. No response at all, or small contractions, were found in response to electrical stimulation in K+ (35 mM)-contracted detrusor strips. Detrusor preparations contracted by carbachol were concentration-dependently relaxed by exogenously administered NO, SIN-1 (NO-donor), and isoprenaline, whereas vasoactive intestinal polypeptide had minor effects. NO and SIN-1 induced maximal relaxations of 63 +/- 3% and 70 +/- 4%, respectively, of the tension induced by carbachol. Isoprenaline produced an almost complete relaxation (96 +/- 4%).7. The results suggest that NANC-nerve mediated relaxation, involving the L-ARG/NO pathway, can be demonstrated consistently in the pig trigonal and urethral, but not in detrusor smooth muscle. The importance of this pathway for lower urinary tract physiology and pathophysiology remains to be established.
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PMID:Nitric oxide and relaxation of pig lower urinary tract. 139 68

The amygdaloid complex participates in the modulation of endocrine functions, and contains measurable amounts of noradrenaline (NA) and dopamine (DA). This study examined the contribution of the amygdaloid catecholaminergic systems to the regulation of the adrenal medulla and the ovary. To accomplish this the neurotoxin 6-hydroxydopamine (6-OHDA) was bilaterally injected into the basolateral nucleus of the amygdala (ABL) in cycling rats. The contents of NA and DA in right and left amygdala decreased significantly in lesioned animals with respect to sham lesioned animals, but hypothalamic levels were not different between groups. Administration of 6-OHDA to rats increased the NA, DA and adrenaline (A) contents of the adrenals compared to vehicle treated rats. In addition, lesioned animals showed a significant increase of NA and DA contents in the ovary, although A levels did not differ between groups. Serum oestradiol (O) concentrations were significantly lower in lesioned animals than in controls. These data suggest that the amygdaloid catecholaminergic systems exert an inhibitory effect on catecholamine content of the adrenals and the ovary, and influence the ovarian oestradiol secretion mechanism.
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PMID:Influence of amygdala catecholamines on ovarian and adrenal medullary secretion. 162 26

Treatment of EMT 6 mammary adenocarcinoma cells with Interferon-gamma (IFN-gamma, 10 U.ml-1) plus endotoxin lipopolysaccharide (LPS, 100 ng.ml-1) induces concomitantly a growth arrest and production of citrulline and nitrite from L-arginine. A similar L-arginine-dependent metabolism is responsible for the vascular smooth muscle relaxing effect of stimulated endothelial cells. We therefore investigated the ability of EMT 6 cells to induce the relaxation of endothelium-denuded rat aortic rings precontracted with noradrenaline (1 microM). Pretreatment of EMT 6 cells with IFN-gamma + LPS increased their relaxing potency by 5-10 times. The relaxin effects of control and treated EMT 6 cells were entirely counteracted by NG-monomethyl-L-arginine (300 microM), a specific inhibitor of nitrite and citrulline production from L-arginine, and by methylene blue (10 microM) and LY 83583 (10 microM), two inhibitors of NOo-induced activation of guanylate cyclase. The effect of NG-monomethyl-L-arginine was reversed by L- but not D-arginine (1 mM). It is concluded that IFN-gamma + LPS increase the production of a relaxing factor in EMT 6 cells through the L-arginine-NOo-synthase pathway.
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PMID:Production of an arginine-derived relaxing factor induced by IFN-gamma plus endotoxin in murine adenocarcinoma EMT 6 cells. 212 6

The antistress affect of the substance P1-4 N-terminal fragment (ARG-Pro-Lys-Pro, 100 mkg/kg, i.p.) has been studied on the model of immobilization stress in rats. It was ascertained that the preparation of protective effect is revealed to the greatest extent on the exhaustion stage (48 h of immobilization), which served to prevent the lymphoid organs mass reduction and ulcer development and also accounted for greater adrenaline and noradrenaline content preservation in tissues and chromaffin cells of adrenal glands in stressed animals.
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PMID:[Effect of the N-terminal fragment of substance P1-4 on the somatic manifestations of the stress reaction and on the catecholamine content of the adrenals in rats]. 246 99

The effect of ganglionic blockade (GB) and subsequent i.v. infusion of adrenaline (AD), noradrenaline (NA), isoproterenol (IP), and angiotensin II (AII) on thoracic duct lymph flow (LF) and transcapillary escape rate of plasma proteins (FER) was studied in anaesthetized (Nembutal), paralyzed (pancuronium), and artificially ventilated dogs. The carotid artery, the external jugular vein, and the thoracic duct were cannulated. Following a control period, GB was performed by pentolinium tartrate and thereafter the other drugs were infused in a random sequence for 30-60 min with 1 h intervals. Mean arterial blood pressure was decreased from 125 to 90 mmHg by GB, it was increased by 36 mmHg by AD, 41 mmHg by NA, and 44 mmHg by AII, and was decreased by 27 mmHg by IP. LF was about 38 microliter/min/kg before GB and was not changed systematically by GB, because either the sympathetic tone was rather weak or the intrinsic contractions and the tone of lymphatics were reduced by GB. FER was not affected by GB. LF increased by 9 microliter/min/kg (control 36 microliter/min/kg) during AII infusion, probably due to increased lymph formation; the latter can be concluded from the 68% increase in FER. NA raised LF by 15 microliter/min/kg (control 44 microliter/min/kg) probably due to alpha-adrenergic stimulation of the intrinsic contractions of lymphatics; lymph formation seemed not to be affected because FER was not changed systematically. AD enhanced LF by 29 microliters/min/kg (control 39 microliters/min/kg).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Effect of ganglionic blockade and subsequent i.v. infusion of catecholamines and angiotensin II on the formation and transport of lymph. Studies in anesthesized dogs and a review of the literature]. 382 39

First, it was confirmed that bilateral lesions in the basolateral region of the amygdala (ABL) of the rat increased the time spent eating novel as compared to familiar food in a food preference test, and that the lesions impaired learned taste aversion to a sucrose solution which had been paired with lithium chloride. Then the roles of noradrenaline and serotonin in the amygdala in these aspects of food intake were investigated. In Experiment 2, it was shown that injections of 10 and 20 nmoles of noradrenaline (NA) into the ABL increased the time spent eating familiar food in the food preference test. Higher doses of NA (50 and 100 nmoles) increased the total time spent eating without changing the preference of the rats for familiar or novel food, and produced behavioral side effects. Serotonin (5HT) injected into the ABL in doses of 10, 50 and 100 nmoles did not modify the pattern of choice of the foods. In Experiment 3, it was shown that depletion of NA in the ABL with 10 micrograms 6-hydroxydopamine did not alter the level of feeding of novel and familiar foods, but did impair taste aversion Depletion of 5HT in the ABL with 10 micrograms 5,7 dihydroxytryptamine did not alter food preferences or impair the taste aversion learning. The depletions of NA and 5HT were confirmed biochemically. These results provide further evidence for a role of the amygdala in preferences for novel as compared to familiar foods and in learning that the ingestion of a food is associated with sickness, and suggest that noradrenaline but not serotonin in the amygdala is involved in these types of control of food intake.
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PMID:Role of noradrenaline and serotonin in the basolateral region of the amygdala in food preferences and learned taste aversions in the rat. 609 45

The contractile activity of smooth-muscle strips (15 X 2 mm), isolated from the internal anal sphincter [IAS] of chloralose-anaesthesized cats, was recorded under isometric conditions. The relaxation effects of exogenously applied acetylcholine (Ach) and nicotine (Ns on cat IAS turn into contractile after treatment of the preparations with depolarizing agent (increased [K+]0 scorpion venom, ouabaine). These contractile effects are blocked completely by phentolamine, guanetidine, hexamethonium and they are antagonized by TTX. Relatively high N concentrations induce a three-phase effect whose second contractile component is phentolamine- and guanethidine-sensitive. Field electrical stimulation (FES - 0.7-20 Hz, 0.1 ms, 40 V, duration 15 s) induces biphasic response in IAS: initial contraction which increases after an increase in [K+]0 and is blocked by phentolamine and guanethidine, with subsequent relaxation which is not affected by adrenergic and cholinergic blockers. The effects of FES are TTX-sensitive. The article discusses the problem of the release of noncholinergic nonadrenergic inhibitory neurotransmitter and of noradrenaline by means of presynaptic N-cholinergic receptors. It is assumed that the correlation in which the two transmitters are released depends on the different threshold value of the membrane potential of the nerve terminals, whereby excitatory-secretion coupling takes place.
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PMID:Modulation of the release of noradrenaline and of noncholinergic, nonadrenergic inhibitory neurotransmitter through presynaptic N-cholinergic receptors by means of depolarizing agents in cat internal anal sphincter. 614 35

A lot of over 60 atherosclerotics with clinical manifestations of senile depressive illness was studied comparatively with a lot of subjects of the same age with essential arterial hypertension (EAH). As concerns the behaviour of the catecholamine content in CSF and blood, the total catecholamines are approxiately equal in the two lots, but with a clear difference of the catecholamine fractions. The CSF catecholamines behaviour in old atherosclerotics is characterized by the presence of increased values of noradrenaline (NA) and of adrenaline (A), with increased statistical significance, but without modifications of the adrenaline percentage (A %) from the total catecholamines, comparatively to the values found in normal subjects. The serotonin (5-HT) content of the CSF in men with atherosclerotic senile depressive illness was lower even than in subjects with coronary atherosclerosis. In atherosclerosis protides modifications precede the histologic changes. In CSF, GLU, ALA, TYR increase in old subjects. In blood, GLU, ALA, TYR, HIS, LEU, SER increase in the same subjects. ARG decreases with age. THR is higher in men than in women. In the urine of all the men as well as of all the women of more than 60 years, GLN and ALA have increased values. LYS increases with age. GLN and ARG are higher in men than in women.
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PMID:Pattern of the cerebrospinal fluid (CSF) and blood biogenic amines and of the CSF, blood and urine amino acids as pathogenetic ground of the senile depressive illness. 677 91

It is unknown whether the catecholamine (CAT) response to acute exercise and prolonged training in humans with spinal cord injury (SCI) is similar to that of neurologically intact man. Plasma samples were collected from seven subjects with chronic SCI (level of injury C5-T7) at rest and during voluntary arm-crank ergometry (ACE) before and after 6 months of training with functional electrical stimulation cycle ergometry (FES-CE). Similar plasma collections were made during one FES-CE exercise training session after 6 months of training. Norepinephrine (NE) and epinephrine (EPI) were measured by HPLC. After FES-CE training, resting NE decreased 37% (950 +/- 150 vs 1510 +/- 350 pmol.l-1 pretraining); resting EPI decreased 80% (54 +/- 10 vs 163 +/- 32 pmol.l-1 pretraining) (P < 0.05 by paired t-tests). No significant changes were observed in group means after training for the CAT response to submaximal ACE; however, five of seven subjects exhibited greater increments in plasma NE with ACE after FES-CE training. Acute FES-CE exercise elicited a 55-844% increase in NE, and a 35-350% increase in EPI above resting values with power outputs eliciting heart rates of 90-146 bpm. These data provide evidence for a systemic CAT response in subjects with SCI during acute FES-CE and reduced resting CAT following 6 months of training with FES-CE.
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PMID:Catecholamine response to exercise and training in individuals with spinal cord injury. 779 64

The effects of subchronic (30 days) drinking water exposure of rats to ZnSO4 or Pb(CH3COO)2 alone or in combination on the adrenergically-mediated contractile responses of isolated vas deferens were studied. The contractile effects of the alpha 1, alpha 2-adrenoceptor agonist noradrenaline (NA) and to the alpha 1-adrenoceptor agonist 1-phenylephrine (1-PhE) were decreased after zinc exposure, whereas after lead exposure or lead plus zinc exposure they were not changed. The contractile responses to field electrical stimulation (FES, 0.1 Hz, 1 msec, 80 V) were diminished in amplitude in all metal-treated preparations as compared to controls. The yohimbine-induced restoration of the clonidine inhibited contractions in response to FES was decreased in both lead- and zinc-treated preparations, the EC50 for yohimbine being 0.018 +/- 0.001 microM in control preparations, 0.073 +/- 0.019 microM in lead-treated preparations and 0.056 +/- 0.021 microM in zinc-treated preparations. The calcium-channel blocker verapamil was found to inhibit at low concentrations and to increase at higher concentrations the FES-induced contractile responses in preparations from zinc-exposed rats. The inhibitory effect of cumulatively applied nitrendipine on the FES-induced contractions was increased in both lead- and zinc-treated smooth muscles, but was not altered in the preparations from lead plus zinc-treated rats. Therefore, subchronic exposure to subtoxic doses of lead of zinc led to different changes in the adrenergically-mediated contractility of isolated vas deferens. The changes induced by zinc exposure were not observed after lead plus zinc exposure. All these findings might be of pharmacological, toxicological or clinical importance.
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PMID:Effects of subchronic exposure of rats to lead or zinc on alpha-adrenoceptor-mediated contractile responses in isolated vas deferens. 820 81


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