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N Turner

Publications and source records attributed to N Turner.

68 records · Page 4Linked to original sources

Sgd 101/75: a sympathomimetic that can be used to identify a new subtype of alpha-adrenoceptor, the alpha 1s-adrenoceptor.

When Sgd 101/75 was compared with clonidine in a number of tests for CNS activity, Sgd 101/75 exhibited little activity in any test. Sgd 101/75 raised BP without affecting HR in several species of anaesthetised animals. The rise in BP was subject to tachyphylaxis, could be antagonised by alpha 1-adrenoceptor antagonists, and was obtainable in reserpinised animals. The vasopressor effect of NA was antagonised by Sgd 101/75. Thus Sgd 101/75 is a directly acting partial agonist for vascular alpha 1-adrenoceptors. On the coaxially stimulated guinea-pig ileum and field stimulated rat vas deferens, the twitch response to single pulse stimulation was reduced by NA or clonidine stimulating prejunctional alpha 2-adrenoceptors. Sgd 101/75 antagonised these inhibitory effects competitively (pA2 for antagonism of clonidine on the vas = 6.12). Sgd 101/75 acted as a specific partial agonist on the alpha 1-adrenoceptors of the guinea-pig taenia caecum that subserve relaxation of this tissue. Sgd 101/75 was a full agonist on the alpha 1-adrenoceptors of the rat anococcygeus in vitro. Phenoxybenzamine (300 pM for 30 min, followed by 20 washes over the next 30 min) reduced contractions of the anococcygeus to Sgd 101/75, but produced little inhibition of NA-induced contractions. In phenoxybenzamine-pretreated preparations, Sgd 101/75 (400 microM) did not antagonise NA (maximal effect and EC50 values not changed significantly), so it was concluded that Sgd 101/75 and NA interact with different alpha 1-adrenoceptor subtypes in this tissue. The subtype specifically activated by Sgd 101/75 was designated the alpha 1s-adrenoceptor. The mouse anococcygeus contained alpha 1s-adrenoceptors, whereas this receptor was absent from the rabbit anococcygeus.

Adrenergic alpha-Agonists↗

The effects of ethionine administration and choline deficiency on protein carboxymethylase activity in mouse pancreas.

Protein carboxymethylase of mouse pancreas is both soluble (70%) and particulate (30%). The Km for S-adenosylmethionine is 7.5 x 10(-7) M and the Ki for S-adenosylethionine is 1.3 . 10(-5) M. Administration of an ethionine containing diet results in a decrease in protein carboxymethylase activity. Ethionine ingestion also increases pancreatic amylase content by interfering with digestive enzyme discharge. The reciprocal changes in amylase content and protein carboxymethylase activity can be detected within 12 h of commencing the ethionine administration and are enhanced by simultaneous choline deficiency. These studies support the hypothesis that protein carboxymethylase plays an important role in secretion of exportable material. Inhibition of pancreatic protein carboxymethylase activity in vivo may be one important mechanism by which ethionine interferes with digestive enzyme discharge.

Adenosine↗

Biochemical transformation by temperature-sensitive mutants of herpes simplex virus type 1.

Biochemical transformation assays of herpes simplex virus type 1 temperature-sensitive (ts) mutants distinguished three groups of mutants with regard to their thymidine kinase (TK) transforming ability: those incapable of transferring the TK gene at either the permissive or restrictive temperatures (group I); those resembling the wild-type virus, and therefore able to transform at both the permissive and nonpermissive temperatures (group II); and those that failed to transform or exhibited very low transformation frequencies at the permissive temperature but were able to transform at the nonpermissive temperature (group III). Two mutants in group II exhibited greatly enhanced transformation efficiency at the permissive temperature. The ts lesions in the majority of the mutants tested map between 0.30 and 0.60 units on the viral genome. Mutants with TK-positive (TK+), but DNA-negative, phenotypes at the nonpermissive temperature produced no TK+ transformants at the permissive temperature and only unstable transformants at the nonpermissive temperature. This suggests that a function which is required for viral DNA synthesis is also required to obtain stable expression or to transfer the TK+ gene or both when transfer is mediated by the entire viral genome.

Cell Line↗

Effect of diethylstilbestrol on replication and transformation by human herpesviruses.

Human embryo fibroblasts treated with diethylstilbestrol (DES) gave rise to slightly increased plaque production by cytomegalovirus (CMV): plaques were also slightly larger in treated cells when compared to those in untreated cultures. There was no significant enhancement of plaque production by herpes simplex virus (HSV) types 1 and 2 in the human cells or in primary rabbit kidney cells treated with DES. Growth analyses of HSV and CMV in DES-treated cells failed to reveal enhancement of virus production when compared to untreated cells. The frequency of biochemical transformation of mouse cells deficient in thymidine kinase (TK) to the TK+ phenotype by HSV was markedly enhanced when cells were pretreated with DES. TK+-transformed colonies arising from DES-treated cells were also larger than those derived from untreated cultures. These reveal that DES increases susceptibility of human cell lines to CMV infection and enhances efficiency of biochemical transformation of mouse cells by HSV.

Animals↗

Biochemical Transformation of mouse cells by herpes simplex virus types 1 and 2: comparison of different methods for inactivation of viruses.

Comparison of methods to inactivate lytic properties of herpes simplex viruses revealed that ultraviolet irradiation, photodynamic procedures, and heat all destroyed infectivity effectively. Ability to biochemically transform thymidine kinase deficient cells to an enzyme positive phenotype was retained after limited exposure to heat or ultraviolet light but appeared to be destroyed by photodynamic methods employing neutral red. Exposure to 56 degrees C quickly and effectively destroyed transforming activity with lower temperatures being less effective. The most reproducible transforming assays were obtained following inactivation by ultraviolet light. Cell cultures developed by this procedure were virus-free but retained ability to synthesize virus-specific antigens.

Animals↗

The effects of ATP-receptor blocking agents on the response to the guinea-pig isolated bladder preparation to hyoscine-resistant nerve stimulation.

The effects of very high concentrations of quinidine, imidazole and phentolamine were investigated on the responses of the guinea-pig isolated bladder to nerve stimulation in the presence of hyoscine in an attempt to determine whether or not ATP mediated the contractions. Quinidine reduced the response to nerve stimulation without affecting the histamine controls, though this was probably due to a local anaesthetic effect. Imidazole potentiated the response to histamine. Phentolamine and two experimental drugs (2-2' pyridylisatogen and 2-2' methoxyphenylisatogen) that are active against ATP-induced relaxations of the guinea-pig isolated taenia were nonspecific in their blockade of the contractions of the bladder to nerve stimulation.

Adenosine Triphosphate↗

The evolution of endothermy: role for membranes and molecular activity.

On the basis of the comparative approach and three models of metabolism (endothermic and ectothermic vertebrates, body mass, and mammalian development), we suggest that a few common cellular processes, linked either directly or indirectly to membranes, consume the majority of energy used by most organisms; that membranes act as pacemakers of metabolism through changes in lipid composition, altering membrane characteristics and the working environment of membrane proteins--specifically, that changes in the membrane environment similarly affect the molecular activities (specific rates of activity) of membrane-bound proteins; and that polyunsaturation of membranes increases whereas monounsaturation decreases the activity of membrane proteins. Experiments designed to test this theory using the sodium pump support this supposition. Potential mechanisms considered include fluidity, electrical fields, and related surface area requirements of lipids. In considering the evolution of endothermy in mammals, for example, if the first mammals were small, possibly nocturnal and active organisms, all these factors would favour increased polyunsaturation of membranes. Such changes (from monounsaturated to polyunsaturated membranes) would allow membranes to set the pace of metabolism in the evolution of endothermy.

Animals↗