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J N Davis

Publications and source records attributed to J N Davis.

At least 109 records · Page 6Linked to original sources
PubMed1980

Identification and characterization of adrenergic receptors and catecholamine-stimulated adenylate cyclase in hog pial membranes.

In order to define the adrenergic receptors in small pial blood vessels, we studied [3H]dihydroalprenolol (DHA) binding, [3H]dihydroergocryptine (DHE) binding, and catecholamine-stimulated adenylate cyclase in membranes prepared from the hog pia. [3H]dha bound to a saturable number of sites (0.09 pmol/mg protein) with a high affinity to (10 mM). The ability of a small series of adrenergic agents to compete for [3H]DHA binding was as expected for binding to beta-adrenergic membrane receptors. The receptor binding appeared to be composed largely of beta 2-adrenergic sites but some sites with beta 1 properties were detected. The beta-adrenergic agonist, isoproterenol, stimulated adenylate cyclase activity by 20% in pial membranes in the presence of GTP. The potency of catecholamines in stimulating adenylate cyclase correlated well with theif sites (0.39 pmol/mg) on these membranes. alpha-Adrenergic agents were potent competitors for [3H]DHE binding but dopamine, serotonin and histamine had effects only at high concentrations. These data demonstrate the presence of alpha- and beta-adrenergic membrane receptors and beta-adrenergically stimulated adenylate cyclase activity in small pial blood vessels from the hog.

Adenosine Triphosphate↗
PubMed1980

Hippocampal alpha- and beta-adrenergic receptors: comparison of [3H]dihydroalprenolol and [3H]WB 4101 binding with noradrenergic innervation in the rat.

The relationship of alpha- and beta-adrenergic receptors to the noradrenergic innervation of the rat hippocampal formation was studied with histofluorescent, biochemical, and radioligand binding methods. The dentate gyrus received a major portion of the innervation and contained twice the norepinephrine content of the hippocampal gyrus. However, the density of beta-adrenergic receptors, determined by [3H]dihydroalprenolol (DHA) binding, was approximately equal in both gyri. By contrast, a presumed alpha-adrenergic binding site was relatively concentrated in the dentate gyrus, roughly correlating with the distribution of the noradrenergic innervation. Although a significant concentration of beta-adrenergic receptors in the pyramidal cell layer had been suggested in previous studies with fluorescent analogs of propranolol, direct microchemical measurements of [3H]DHA binding in stratum pyramidalis and stratum radiatum showed that beta-adrenergic receptors were uniformly distributed in the hippocampal gyrus. These data, demonstrating a ubiquitous distribution of beta-adrenergic binding in a brain region with a well-defined noradrenergic input, suggest that a portion, perhaps a majority, of beta-adrenergic receptors are not associated with noradrenergic nerve terminals.

Alprenolol↗
PubMed1980

Lymph nodes--a possible site for sympathetic neuronal regulation of immune responses.

Noradrenergic fibers were identified in rat cervical lymph nodes by fluorescence histochemistry and confirmed by radioenzymatic determination of norepinephrine. After superior cervical ganglionectomy, lymph node norepinephrine and noradrenergic fluorescence were strikingly decreased. The alpha-adrenergic radioligand [3H] dihydroergocryptine bound to saturable sites on lymph node membranes (0.20 pmol/mg protein; affinity constant, 8 nM) with characteristics expected for alpha-adrenergic receptor binding. The alpha-adrenergic binding sites were present in high concentration in membranes from lymph node stroma but were negligible in membranes of lymphocytes teased from nodes. In lymph nodes the ratio of alpha-adrenergic binding sites to norepinephrine content was higher than ratios of many other sympathetically innervated tissues such as iris or vas deferens. The presence of sympathetic innervation and the high concentration of alpha-adrenergic binding sites relative to that innervation suggest that the sympathetic nervous system modulates an intrinsic lymph node function through alpha-adrenergic mechanisms.

Adrenergic Fibers↗
PubMed1980

Subunit interaction of adenylylated glutamine synthetase.

The glutamine synthetase (GS) activity in Escherichia coli is regulated by a bicyclic interconvertible enzyme cascade which involves the cyclic adenylylation (inactivation) and deadenylylation (activation) of GS on the one hand, and the modulation of these processes by the uridylylation and deuridylylation of Shapiro's regulatory protein on the other. The specific activity of GS in a given metabolic state is determined by the fraction of its subunits that are adenylylated, and this fraction is determined by the concentration of over 40 metabolites. Through allosteric and substrate interactions with one or more of the cascade enzymes, these metabolites alter the rates of the covalent modification and demodification reactions. By means of immunoprecipitation studies with anti-AMP specific antibodies, it has been established that the partially adenylylated glutamine synthetase, which is present in a given steady state, is a mixture of hybrid molecules containing different numbers and possibly distributions of adenylylated subunits. Partial separation of these hybrid mixtures has been achieved by affinity chromatography on Affi-Blue Sepharose columns. From immunochemical studies it is evident that anti-AMP antibodies can react with adenylylated subunits of all molecular species of GS, but that the capacities of these primary antigen-antibody reactions to yield precipitable aggregates is very dependent of the number of adenylylated subunits per molecule, and much less so upon the total concentration of adenylylated subunits present. the studies suggest that precipitability is a function either of the distribution of adenylylated subunits within hybrid species, or of the kinetics of intra- vs intermolecular bivalent interactions.

Glutamate-Ammonia Ligase↗
PubMed1979

beta-Adrenergic receptor regulation by agonists and membrane depolarization in rat brain slices.

Rat cerebral cortex slices exposed to (-)-isoproterenol and then washed accumulated significantly less cyclic AMP when rechallenged with isoproterenol than did control slices. The isoproterenol-induced desensitization was associated with a concurrent reduction in [3H]dihydroalprenolol membrane binding but with no change in the affinity of [3H]dihydroalprenolol or isoproterenol for the binding sites. beta-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, batrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetrodotoxin or by removing Na+ from the buffer. These data demonstrate partial participation of the membrane receptor in beta-adrenergic desensitization of rat brain slices and suggest that brain beta-adrenergic receptors, like cholinergic receptors in skeletal muscle and alpha-adrenergic receptors in rat parotid, are regulated in part by membrane voltage.

Animals↗
PubMed1979

Denervation-induced changes in alpha and beta adrenergic receptors of the rat submandibular gland.

Denervation resulted in a marked increase in the beta adrenergic response and isoproterenol-stimulated cyclic adenosine 3':5'-monophosphate accumulation of dispersed cells prepared from a rat submandibular gland. This increase in beta adrenergic response was paralleled by an increase in the density of beta adrenergic receptors in membranes prepared from these glands. Denervation also produced a moderate increase in alpha adrenergic receptor density in membranes prepared from whole glands. However, the alpha adrenergic response in cells, epinephrine-induced release of potassium, appeared unaltered by denervation. Furthermore, membranes prepared from denervated dispersed cells did not show the increase in alpha adrenergic receptor density seen in membranes from an intact denervated gland. These data demonstrate that removal of noradrenergic nerve terminals affects alpha and beta adrenergic receptors differently. While it is clear that beta adrenergic membrane receptors participate in denervation-induced supersensitivity, the changes in alpha adrenergic membrane receptors are more complex and may not contribute to the supersensitivity seen after denervation. On the basis of competitive binding studies, the adrenergic receptors in membranes from intact submandibular glands were subclassified as beta-1 and alpha-2. Denervation did not alter the binding characteristics of the alpha-2 receptors in this gland, demonstrating that alpha-2 adrenergic membrane receptors can be postsynaptic in this adrenergically innervated tissue.

Animals↗
PubMed1978

Brain alpha-adrenergic receptors: comparison of [3H]WB 4101 binding with norepinephrine-stimulated cyclic AMP accumulation in rat cerebral cortex.

The ability of a series of adrenergic agents to displace the binding to brain membranes of [3H]WB 4101, a potent alpha-adrenergic antagonist (WB 4101 = 2-[2-(2,6-dimethoxyphenoxy)ethylaminomethyl]-1,4-benzodioxane hydrochloride), has been compared with the potency of these agents in stimulating or inhibiting the alpha-adrenergic component of cyclic AMP accumulation in rat cerebral cortex slices. [3H]WB 4101 rapidly bound to a high affinity site (KD = 2.7 nM) in membranes from cerebral cortex. Binding came to equilibrium by 2 min at 37 degrees C and was rapidly reversed in the presence of phentolamine. The potencies of adrenergic agents (WB 4101 greater than phentolamine greater than naphazoline) in displacing binding of [3H]WB 4101 were comparable to the potencies of these agents as inhibitors of the alpha-adrenergic component of norepinephrine-stimulated cyclic AMP accumulations. Phenoxybenzamine, clonidine, chlorpromazine and haloperidol were about 10--30 times more potent in inhibiting cyclic AMP accumulation than in displacing [3H]WB 4101 binding. The potency of classical alpha-adrenergic agonists in displacing WB 4101 (epinephrine greater than norepinephrine greater than methoxamine) correlated with the ability of these agonists to increase cyclic AMP levels. Overall a significant correlation (r = 0.87, P less than 0.005) was found between WB 4101 binding and alpha-adrenergically mediated cyclic AMP accumulation in brain. Several ligands bind to specific sites in brain membranes with alpha-adrenergic receptor properties. The identification of these binding sites as receptors depends on a correlation of binding with a known alpha-adrenergic receptor-mediated response in brain. These data demonstrating that WB 4101 correlates with norepinephrine-stimulated cyclic AMP accumulation suggest that WB 4101 may bind to the membrane receptor sites mediating the alpha-adrenergic accumulation of cyclic AMP in rat cerebral cortex.

Adrenergic alpha-Antagonists↗