Disease relevance of NECA

• Pertussis toxin completely abolished promotion of chemotaxis by CPA but enhanced inhibition by NECA of O2- generation [1].
• Hepatocellular carcinoma cells treated with NECA at a concentration range of 10(-7) M to 5 x 10(-5) M for one hour in a hypoxic atmosphere also had significantly higher cAMP levels than that of hypoxia controls [2].
• The non-selective but A(2b)-potent adenosine agonist 5'-(N-ethylcarboxamido)adenosine (NECA) infused from 5min before to 1h after reperfusion mimicked postconditioning's effect on infarct size (17.2+/-2.7% infarction) and MRS 1754 blocked the NECA-induced cardioprotection, confirming that A(2b) activation was protective [3].
• 2. NECA (0.01-1 microgram, i.c.v.), all of the A1-selective agonists (0.01-1 microgram, i.c.v.) and APNEA (0.1-3 micrograms i.c.v.) produced profound and dose-related hypothermia and sedation [4].
• DPCPX blunted the bradycardia associated with CCPA and NECA, whereas ZM-241385 attenuated their hypotensive effects [5].

Psychiatry related information on NECA

• The locomotor activity depression elicited by NECA and CHA was reversed by A1-selective antagonists [6].
• Moreover, the combinations of LY 300164 with either NECA or APNEA were devoid of motor impairment, although they produced a significant long-term memory deficit [7].
• CGS21680, APEC, and NECA produced significant increases in the total amounts of non-rapid-eye-movement (NREM) sleep and rapid-eye-movement (REM) sleep after at least one dose within the range of administration rates [8].

High impact information on NECA

• Higher doses of apomorphine elicited a self-mutilatory response after the injection of NECA into the caudate nucleus [9].
• Adenosine receptor analogues, 5'N-ethylcarboxamidoadenosine (NECA) and N6-phenylisopropyladenosine (PIA), also promoted chemotaxis; the order of agonist potency was consistent with that of an A2 adenosine receptor (NECA greater than PIA greater than or equal to adenosine) [10].
• A potent antagonist at adenosine receptors, 8-p-sulfophenyltheophylline (10 microM), completely reversed NECA enhancement of chemotaxis but did not affect chemotaxis by itself [10].
• NECA also promoted chemotaxis quantitated by a different technique, chemotaxis under agarose, to the surrogate bacterial chemoattractant FMLP [10].
• Additionally, CPA (A1 agonist) did not increase binding of [3H]FMLP to the cytoskeleton as well as NECA (A2 agonist) [1].

Chemical compound and disease context of NECA

• In R226 stably transfected CHO cells, adenosine agonists R-PIA, NECA, and CGS21680 inhibited by 40-50% the forskolin-stimulated cAMP accumulation through a pertussis toxin-sensitive G protein with an EC50 of 18 +/- 5.6 nM, 23 +/- 3.5 nM, and 144 +/- 34 nM, respectively [11].
• We had previously shown that Ag and NECA both activate phospholipase C but by different mechanisms; cells that had been treated with cholera or pertussis toxin, for example, responded to Ag but not to NECA with the release of inositol phosphates, increase in levels of cytosolic Ca2+, and secretion [12].
• In contrast to NECA, antigen stimulation resulted in a pertussis toxin-resistant, sustained hydrolysis of inositol phospholipids, increases in free intracellular Ca2+, accelerated influx of 45Ca2+, and secretion from RBL-2H3 cells [13].
• Calcium responses to NECA and CPA were inhibited by 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A(1) receptor antagonist, and by pertussis toxin (PTX) [14].
• 8-SPT-resistant falls in blood pressure are also seen, in the absence of bradycardia, with 5'-N-ethylcarboxamidoadenosine (NECA) and the R- and S-enantiomers of N6-phenylisopropyladenosine (PIA) [15].

Biological context of NECA

• Competitive binding studies reveal the appropriate A2 receptor pharmacologic potency order with 5'-N-ethylcarboxamidoadenosine (NECA) greater than (-)-N6-[(R)-1-methyl- 2-phenylethyl]adenosine (R-PIA) greater than (+)-N6-[(S)-1-methyl-2- phenylethyl]adenosine (S-PIA) [16].
• FMLP (0.1 mumol/L) increased GTPase activity by 31.9 +/- .9 pmol/mg/min, an increment that was markedly inhibited to approximately 50% of control by NECA (IC50 = 3 nmol/L, P less than .001, n = 5) and isoproterenol (IC50 = 30 nmol/L, P less than .001, n = 5) [17].
• Action potential duration at 50% repolarization was not altered by WRC-0090, NECA, or WRC-0013 with or without 0.1 microM DPCPX or pertussis toxin pretreatment, and WRC-0090 and NECA failed to prolong the action potential duration of myocytes exposed to 0.1 or 1 microM forskolin [18].
• In vitro autoradiographic techniques were used to characterize binding sites for 3H-cyclohexyladenosine (CHA) and 3H-5'-N-ethylcarboxamidoadenosine (NECA) in cat and kitten visual cortex [19].
• Cellular exposure to NECA induces rapid (t1/2 = approximately 1 min) A3AR phosphorylation on serine and threonine residues [20].

Anatomical context of NECA

• N6-Cyclopentyladenosine (CPA), a selective A1 agonist, promoted neutrophil chemotaxis to the chemoattractant FMLP as well as or better than 5'N-ethylcarboxamidoadenosine (NECA) [1].
• NECA significantly increased association of [3H]FMLP with cytoskeletal preparations as it inhibited O2-. Disruption of microtubules did not prevent NECA from increasing association of [3H]FMLP with cytoskeletal preparations [1].
• WRC-0090 alone or with 0.1 microM DPCPX did not increase the amplitude of shortening of pertussis toxin-treated or untreated myocytes, and WRC-0090 or NECA did not significantly increase cAMP accumulation [18].
• NECA inhibited cytosolic protein phosphatase activity by 78 +/- 12% (p < 0.003, n = 6) but did not shift pp1 catalytic subunit from cytosol to plasma membrane [21].
• HIF-1alpha mRNA levels were increased in LPS-treated macrophages in an NF-kappaB-dependent manner; NECA strongly increased these levels in an A(2A)R-dependent manner [22].

Associations of NECA with other chemical compounds

• Rats rotated to the left when 5'-N-ethylcarboxamide adenosine (NECA) was injected into the left caudate nucleus and apomorphine was administered subcutaneously [9].
• Disruption of microtubules by colchicine or vinblastine also abrogated the enhancement by NECA of chemotaxis whereas these agents did not markedly interfere with inhibition by NECA of O2- generation [1].
• Again, 2-chloroadenosine and NECA reduced IL-beta-induced TNF-alpha production more potently than CPA [23].
• Cyclic AMP levels were increased by NECA, and a direct adenylate cyclase activator (forskolin) also suppressed collagenase gene expression [24].
• For some time after 3T3-F442A cells have differentiated to adipocytes, micromolar concentrations of NECA and PIA continue to increase cyclic AMP to a similar extent to that in preadipocytes, whereas nanomolar concentrations of PIA decrease the stimulatory effects of isoprenaline and forskolin on adenylate cyclase by 50% [25].

Gene context of NECA

• Up-regulation of IL-4 and IL-13 was verified using RT-PCR and ELISA; 10 microM NECA increased IL-13 concentrations in HMC-1 conditioned medium 28-fold, from 7.6 +/- 0.3 to 215 +/- 4 pg/ml, and increased IL-4 concentrations 6-fold, from 19.2 +/- 0.1 to 117 +/- 2 pg/ml [26].
• LPS with NECA strongly up-regulates VEGF expression by macrophages from C(3)H/HeN mice (with intact Tlr4 receptors), but not by macrophages from C(3)H/HeJ mice (with mutated, functionally inactive Tlr4 receptors), implicating signaling through the Tlr4 pathway in this synergistic up-regulation [27].
• Both A(2B) AdoR antagonists diminished activation of ERK by NECA exposure [28].
• VEGF secretion was increased 1.9 +/- 0.04-fold with NECA (10 muM) and 1.7 +/- 0.1-fold with hypoxia (5% O(2)) but 3.8 +/- 0.1-fold when these two stimuli were combined [29].
• The mechanism by which NECA promotes astrocytic IL-6 expression has not been identified [30].

Analytical, diagnostic and therapeutic context of NECA

• Subsequent immunoprecipitation of Gi alpha-subunits indicated that NECA stimulated incorporation of label into both Gi alpha-2 and Gi alpha-3 [31].
• Northern blot analysis demonstrated that the mechanism of action was pre-translational since NECA decreased collagenase, but not stromelysin or tissue inhibitor of metalloproteinases 1 (TIMP-1), messenger RNA levels [24].
• Perfusion with artificial CSF containing 10(-7), 10(-6), or 10(-5) M NECA resulted in a 35, 112, and 187% increase in local CBF, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)[32]
• In separate experiments, the responses of blood pressure and heart rate to microinjection of NECA into the brainstem of rats anaesthetized with methoxyflurane/nitrous oxide were also examined [33].
• 2. 2-Chloroadenosine (2-Cl-Ade), 5'-N-ethylcarboxamideadenosine (NECA) and L-N6-phenylisopropyl-adenosine (L-PIA) all produced dose-dependent, transient increases in tracheal insufflation pressure, with an order of potency (NECA greater than or equal to 2-Cl-Ade much greater than L-PIA) typical of A2-receptor mediated biological responses [34].

References