PubMed · 8818919
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R C Harris. 1996. The macula densa: recent developments.. https://doi.org/10.1097/00004872-199607000-00003
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Behavioral and biochemical studies suggest that a negative interaction exists between adenosine A(1) and dopamine D(1) receptors in the brain and that this may contribute to the psychomotor effects of adenosine receptor agonists and antagonists. We examined the functional significance of A(1) and D(1) receptor subtypes in modulating electrically evoked endogenous GABA release from slices/punches of rat basal ganglia (striatum, globus pallidus, striatum containing globus pallidus, and substantia nigra reticulata) and limbic regions (ventral pallidum and nucleus accumbens). In basal ganglia, stimulation of A(1) receptors with the selective agonist R-PIA (1-100 nM) resulted in a concentration-dependent decrease in GABA release. The selective A(1) antagonist DPCPX (10-100 nM) increased GABA release, suggesting that endogenous adenosine tonically inhibits GABA release. However, in basal ganglia, consistent dopamine D(1) receptor modulation of GABA, release was not observed in response to either D(1) agonists or antagonists. Furthermore, the A(1) receptor-mediated inhibition of GABA release was not changed by concurrent activation of D(1) receptors, thus confirming the lack of D(1) receptor modulation under these conditions. In contrast, in ventral pallidum and nucleus accumbens, stimulation of D(1) receptors with SKF-82958 (1 microM) increased GABA release significantly. The D(1) receptor-mediated increase in GABA release was attenuated by concurrent activation of adenosine A(1) receptors. These results are consistent with the hypothesis that an antagonistic A(1)/D(1) receptor interaction may be important in modulating GABA release in limbic regions.
Quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) are methods for anatomic assessment of stent deployment. Intracoronary Doppler is primarily a method for the physiologic assessment of coronary stenoses. It correlates well with traditional noninvasive measurements of lesion significance. Intracoronary Doppler was used for the anatomic assessment of de novo coronary artery stenosis with variable success; however, its use for anatomic assessment of adequate stent deployment is unavailable. A rapid, automated software program was developed based on a modified continuity equation to calculate the maximal in-stent percent area stenosis by comparing the maximal in-stent velocity to an average reference velocity (proximal and distal). This study was designed to compare the Doppler method of an anatomic assessment with QCA and ICUS in 15 patients. Physiologic success of stent deployment was determined by the distal coronary flow reserve to 24 to 36 microg of intracoronary adenosine. Following successful stent deployment, distal coronary flow reserve increased significantly from a baseline of 1.6 +/- 0.5 to 2.9 +/- 1.1. There was a significant correlation between the maximal in-stent percent area stenosis as measured by Doppler and both QCA (r = 0.78, p <0.01) and ICUS (r = 0.84, p <0.01). This study demonstrates that maximal in-stent percent area stenosis can be measured by intracoronary Doppler and a novel software program. The intracoronary Doppler guidewire method can assess the adequacy of stent deployment using both anatomic and physiologic principles and may supplement other quantitative methodologies.
The synthesis and pharmacological profile of a series of neuroprotective adenosine agonists are described. Novel A(1) agonists with potent central nervous system effects and diminished influence on the cardiovascular system are reported and compared to selected reference adenosine agonists. The novel compounds featured are derived structurally from two key lead structures: 2-chloro-N-(1-phenoxy-2-propyl)adenosine (NNC 21-0041, 9) and 2-chloro-N-(1-piperidinyl)adenosine (NNC 90-1515, 4). The agonists are characterized in terms of their in vitro profiles, both binding and functional, and in vivo activity in relevant animal models. Neuroprotective properties assessed after postischemic dosing in a Mongolian gerbil severe temporary forebrain ischemia paradigm, using hippocampal CA1 damage endpoints, and the efficacy of these agonists in an A(1) functional assay show similarities to some reference adenosine agonists. However, the new compounds we describe exhibit diminished cardiovascular effects in both anesthetized and awake rats when compared to reference A(1) agonists such as (R)-phenylisopropyladenosine (R-PIA, 5), N-cyclopentyladenosine (CPA, 2), 4, N-[(1S,trans)-2-hydroxycyclopentyl]adenosine (GR 79236, 26), N-cyclohexyl-2'-O-methyladenosine (SDZ WAG 994, 27), and N-[(2-methylphenyl)methyl]adenosine (Metrifudil, 28). In mouse permanent middle cerebral artery occlusion focal ischemia, 2-chloro-N-[(R)-[(2-benzothiazolyl)thio]-2-propyl]adenosine (NNC 21-0136, 12) exhibited significant neuroprotection at the remarkably low total intraperitoneal dose of 0.1 mg/kg, a dose at which no cardiovascular effects are observed in conscious rats. The novel agonists described inhibit 6, 7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate-induced seizures, and in mouse locomotor activity higher doses are required to reach ED(50) values than for reference A(1) agonists. We conclude that two of the novel adenosine derivatives revealed herein, 12 and 5'-deoxy-5'-chloro-N-[4-(phenylthio)-1-piperidinyl]adenosine (NNC 21-0147, 13), representatives of a new series of P(1) ligands, reinforce the fact that novel selective adenosine A(1) agonists have potential in the treatment of cerebral ischemia in humans.