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Biomedical subjects

H Carswell

Publications and source records attributed to H Carswell.

At least 19 recordsLinked to original sources
PubMed1999

Genes encoding atrial and brain natriuretic peptides as candidates for sensitivity to brain ischemia in stroke-prone hypertensive rats.

-Previous studies suggested that atrial natriuretic peptide gene (Anp) and brain natriuretic peptide gene (Bnp) are plausible candidate genes for susceptibility to stroke and for sensitivity to brain ischemia in the stroke-prone spontaneously hypertensive rat (SHRSP). We performed structural and functional analyses of these 2 genes in SHRSP from Glasgow colonies (SHRSPGla) and Wistar-Kyoto rats from Glasgow colonies (WKYGla) and developed a radiation hybrid map of the relevant region of rat chromosome 5. Sequencing of the coding regions of the Anp and Bnp genes revealed no difference between the 2 strains. Expression studies in brain tissue showed no differences at baseline and at 24 hours after middle cerebral artery occlusion. Plasma concentrations of atrial natriuretic peptide (ANP) did not differ between the SHRSPGla and WKYGla, whereas concentrations of brain natriuretic peptide were significantly higher in the SHRSPGla as compared with the WKYGla (n=11 to 14; 163+/-21 pg/mL and 78+/-14 pg/mL; 95% confidence interval 31 to 138, P=0.003). We did not detect any attenuation of endothelium-dependent relaxations to bradykinin or ANP in middle cerebral arteries from the SHRSPGla; indeed the sensitivity to ANP was significantly increased in arteries harvested from this strain (WKYGla: n=8; pD2=7. 3+/-0.2 and SHRSPGla: n=8; pD2=8.2+/-0.15; P<0.01). Moreover, radiation hybrid mapping and fluorescence in situ hybridization allowed us to map the Anf marker in the telomeric position of rat chromosome 5 in close proximity to D5Rat48, D5Rat47, D5Mgh15, and D5Mgh16. These results exclude Anp and Bnp as candidate genes for the sensitivity to brain ischemia and pave the way to further congenic and physical mapping strategies.

Amino Acid Substitution↗
PubMed1990

gamma-Aminobutyric acid inhibition of histamine-induced inositol phosphate formation in guinea-pig cerebellum: comparison with guinea-pig and rat cerebral cortex.

1. gamma-Aminobutyric acid (GABA), 2 mM, inhibited basal accumulation of [3H]-inositol monophosphate ([3H]-IP1) in lithium-treated slices of guinea-pig cerebellum preincubated with [3H]-inositol. In contrast, 2 mM GABA stimulated the accumulation of [3H]-IP1 in rat cerebral cortical slices over a 60 min incubation period, but had no significant effect in slices of guinea-pig cerebral cortex. The estimated IC50 for the inhibitory action of GABA in guinea-pig cerebellar slices was 0.52 +/- 0.12 mM. 2. GABA inhibited histamine-induced [3H]-IP1 accumulation in guinea-pig cerebellar slices in a non-competitive manner. The best-fit value for the maximum level of inhibition was 74 +/- 6%. The estimated IC50 for GABA was 0.77 +/- 0.15 mM and was not significantly different from the IC50 for inhibition of the basal accumulation of [3H]-IP1. The response to histamine in guinea-pig and rat cerebral cortical slices was also inhibited by 2 mM GABA. 3. In guinea-pig cerebellar slices 2 mM GABA potentiated histamine-induced [3H]-inositol bisphosphate ([3H]-IP2) accumulation, whereas in both guinea-pig and rat cerebral cortex the effect was inhibition. 4. Isoguvacine and muscimol, GABAA-selective agonists, and (-)-baclofen, GABA(B)-selective, had no significant effect on basal or histamine-stimulated accumulation of [3H]-IPs in guinea-pig cerebellar slices. (-)-Baclofen had only a weak inhibitory effect on [3H]-IP1 accumulation in guinea-pig-cerebral cortex (16 +/- 6% inhibition with 10 microM (-)-baclofen), whereas in rat cerebral cortex (-)-baclofen mimicked the inhibitory effect of GABA. 5. Nipecotic acid (1 mM) had qualitatively similar effects to those of 2mm GABA in guinea-pig cerebellar slices. 6. The competitive GABA uptake inhibitors SK&F 89976-A, SK&F 100330-A and SK&F 100561-A were potent histamine H,-receptor antagonists, as indicated by the inhibition of [3H]-mepyramine binding to homogenates of guinea-pig cerebellum and cerebral cortex. 7. GABA (2 mM) caused a small inhibition (12 + 3%) of [3H]-inositol incorporation into total inositol phospholipids in guinea-pig cerebellar slices, as in rat cerebral cortical slices, whereas 0.2mm histamine caused a small stimulation (15 + 4%). In the presence of both GABA and histamine, [3H]-inositol incorporation was unchanged from basal (101 + 5%). 8. GABA also inhibited [3H]-IP1 formation induced by endothelin-1 in guinea-pig cerebellar slices and increased, but not significantly, the amount of [3H]-IP2 accumulated. This, taken with the inhibitory effect on basal and histamine-stimulated accumulation, suggests that the action of GABA in guinea-pig cerebellar slices may be non-selective and may not be exerted through a specific GABA receptor.

Animals↗
PubMed1987

Differential effect of temperature on histamine- and carbachol-stimulated inositol phospholipid breakdown in slices of guinea-pig cerebral cortex.

Slices of guinea-pig cerebral cortex were incubated with [3H]-inositol at 37 degrees C before exposure to histamine or carbachol at 37 degrees C or 25 degrees C. Histamine-stimulated accumulation of [3H]-inositol 1-phosphate ([3H]-IP1) at 25 degrees C was only 5-7% of that at 37 degrees C, whereas for carbachol the response at 25 degrees C was 45-49% of that at 37 degrees C. The affinity of benzilylcholine, obtained from inhibition of carbachol-induced accumulation of [3H]-IP1 was similar at 25 degrees C and 37 degrees C, but the EC50 for carbachol was lower at 25 degrees C (20 +/- 2 microM) than at 37 degrees C (42 +/- 2 microM). The IC50 for histamine inhibition of [3H]-mepyramine binding to homogenates of guinea-pig cerebral cortex did not differ significantly at 25 degrees C and 37 degrees C. Histamine-induced accumulations of [3H]-IP2 and [3H]-IP3 at 25 degrees C, expressed as a percentage of the accumulation at 37 degrees C, were also much less than the corresponding value for carbachol. These observations imply that the locus or pathway(s) of agonist-induced formation of [3H]-IP1 are not the same for histamine and carbachol.

Animals↗
PubMed1986

Regional variation in the characteristics of histamine H1-agonist mediated breakdown of inositol phospholipids in guinea-pig brain.

The position of dose-response curves for histamine-induced accumulation of [3H]-inositol 1-phosphate ([3H]-IP1) in lithium-treated slices of guinea-pig brain prelabelled with [3H]-inositol differed significantly between cerebellum (EC50 5.1 +/- 1.0 microM) and cerebral cortex (EC50 16.3 +/- 0.7 microM). The Hill coefficients of the curves, 1.33 +/- 0.28 and 1.24 +/- 0.03, respectively, did not differ significantly. 2-Methylhistamine, N alpha,N alpha-dimethylhistamine and betahistine were partial agonists in both cerebellum and cerebral cortex, but all produced a greater percentage of the maximum response to histamine in cerebellar slices. In hippocampal slices the response of the partial agonists was intermediate between that in cerebellum and that in cerebral cortex. The four agonists produced an appreciable accumulation of [3H]-inositol 1-phosphate in cerebellar slices even in the absence of Li+ ion. The EC50 and Hill coefficients characterizing the dose-response curves for the four agonists were the same whether 10 mM LiCl was present or not. The affinity constant for mepyramine inhibition of the histamine-induced response was similar in cerebellum, 4.2 +/- 0.6 X 10(8) M-1, and cerebral cortex, 4.6 +/- 1.0 X 10(8) M-1. Curves of mepyramine inhibition of the responses to a fixed concentration of histamine gave no indication of any second component in the response to histamine in either cerebellum or cerebral cortex. The parameters of histamine inhibition of [3H]-mepyramine binding were similar in homogenates of guinea-pig cerebellum and cerebral cortex. These results indicate that H1-agonist-induced accumulation of IP1 may not be as directly related to agonist-receptor interaction as simple reaction schemes suggest.

Animals↗
PubMed1984

Relative potencies of histamine H1-agonists on guinea-pig tracheal smooth muscle.

The relative potencies of a series of histamine H1-agonists in causing contraction of spirally cut strips of guinea-pig trachea, measured in the presence of cimetidine, indomethacin, methylatropine and propranolol, were similar to those reported on other guinea-pig tissues. However, whereas 2-methylhistamine and N alpha,N alpha-dimethylhistamine are apparently partial agonists in potentiating the adenosine-stimulated accumulation of cyclic AMP in slices of guinea-pig cerebral cortex, on tracheal spirals they are full agonists producing the same maximum contraction as histamine.

Animals↗