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Biomedical subjects

R J Summers

Publications and source records attributed to R J Summers.

At least 145 records · Page 8Linked to original sources
PubMed1982

Role of central beta-adrenoceptors in the control of pentylenetetrazol-induced convulsions in rats.

1 The role of central beta-adrenoceptors in the anticonvulsant effect of beta-adrenoceptor antagonists has been examined. 2 Oral administration of (-)- and (+)-propranolol (0.05-1 mg/kg) and (+/-)-pindolol (0.025-0.5 mg/kg) produced a dose-dependent decrease in duration of convulsions produced by pentylenetetrazol (PTZ 50 mg/kg, i.p.) in rats. 3 At the EC50 level, (-)-propranolol is seven times more effective than the (+)-isomer. 4 Oral administration of (-)-, (+)- or (+/-)-practolol (1-10 mg/kg) or (-)- or (+)-timolol (1-10 mg/kg), two beta-adrenoceptor antagonists that do not penetrate the blood brain barrier, had no significant effect on the duration of PTZ-induced convulsions. 5 Intracerebroventricular administration of (-)-propranolol (0.5 microgram/kg) or (-)-timolol (0.25 microgram/kg) produced highly significant anticonvulsant effects whereas the (+)-isomers at the same dose level were ineffective. (+/-)-Pindolol (0.25 microgram/kg) was also much more effective given by this route than when given orally. The (+)- and (-)-isomers of the beta 1-adrenoceptor selective antagonist practolol (10 microgram/kg) exerted only weak anticonvulsant effects. 6 This study provides evidence that beta-adrenoceptor antagonists exert an anticonvulsant effect through central beta 2-adrenoceptors. At high dose levels, additional anticonvulsant activity is associated with membrane stabilization in those antagonists which possess this property.

Adrenergic beta-Antagonists↗
PubMed1982

A study of alpha 1-adrenoceptors in rat renal cortex: comparison of [3H]-prazosin binding with the alpha 1-adrenoceptor modulating gluconeogenesis under physiological conditions.

1 A comparison has been made of the alpha 1-adrenoceptor controlling gluconeogenesis in tubules from rat renal cortex and [3H]-prazosin binding in membranes prepared from the same tissue under physiological conditions. 2 In renal tubules the alpha-adrenoceptor agonists, oxymetazoline, (--)-noradrenaline, (--)-alpha-methylnoradrenaline and (--)-phenylephrine, stimulated gluconeogenesis from pyruvate. Oxymetazoline was the most potent agonist (EC50 15.7 nM) but produced only 61% of the maximum response elicited by (--)-noradrenaline. 3 The alpha-adrenoceptor antagonists, BE2254, prazosin, indoramin and phentolamine inhibited (--)-noradrenaline-mediated increases in gluconeogenesis. The alpha 1-adrenoceptor selective compounds, BE2254 and prazosin, were the most effective antagonists with KB values of 0.74 and 1.47 nM respectively. 4 [3H]-prazosin binding to membranes prepared from rat renal cortex in physiological saline at 37 degrees C was best described by a two site model. High affinity, but not low affinity sites had characteristics consistent with alpha-adrenoceptors. 5 High affinity [3H]-prazosin binding could be completely displaced by the alpha-adrenoceptor agonists, oxymetazoline, (--)-noradrenaline, (--)-phenylephrine, and (--)-alpha-methylnoradrenaline. Slope factors for the displacement curves were all significantly less than unity. The concentrations of agonists required to displace [3H]-prazosin binding were markedly higher than those required to stimulate gluconeogenesis. 6 High-affinity [3H]-prazosin binding was also displaced by the alpha-adrenoceptor antagonists, prazosin, BE2254, phentolamine and indoramin. Slope factors for the displacement curves were close to unity. Ki values calculated from the binding experiments were very similar to KB values obtained in the gluconeogenesis studies. These results suggest that in rat renal cortex the alpha 1-adrenoceptor labelled by [3H]-prazosin is probably that which stimulates gluconeogenesis.

Adrenergic alpha-Agonists↗
PubMed1982

Pigeons' spatial memory: factors affecting delayed matching of key location.

The delayed-matching-to-sample procedure was modified to study pigeons' spatial memory. Nine pecking keys, arranged as a three-by-three matrix, served as the spatial cues. Trials began with a brief "ready" stimulus (dimming of the houselight). Then a randomly chosen key was lit briefly as a sample. After a short delay the sample key was lit again along with one of the other eight keys. A peck at the key that had served as the sample produced grain reinforcement, where as a peck to the other key produced only the intertrial interval. After delayed matching of key location was learned, the effects of sample and delay duration, number of keys illuminated as sample and comparisons, and organization of three-key samples were studied. Matching accuracy decreased as sample duration decreased, delay increased, the number of locations serving as samples increased, the number and proximity of comparisons increased, and when the three-key samples were "discontinuous" rather than "lines".

Animals↗
PubMed1981

Comparison of [3H]clonidine and [3H]guanfacine binding to alpha 2 adrenoceptors in membranes from rat cerebral cortex.

[3H]Clonidine and a new phenylacylguanidine antihypertensive drug, [3H]guanfacine, bind with a high affinity to alpha 2 adrenoceptors in membranes from rat cerebral cortex. Dissociation curves for [3H]clonidine binding indicated the presence of high and low affinity binding sites, whereas with [3H]guanfacine, two components could be distinguished only with difficulty; the major part of the binding being to a high affinity component. Saturation experiments revealed that both ligands bind with similar high affinity but that [3H]guanfacine labels twice the number of sites labeled by [3H]clonidine.

Animals↗
PubMed1981

Pharmacological investigation of alpha-adrenoreceptors in guinea-pig splenic capsule.

1. A study has been made of alpha-adrenoreceptors in the smooth muscle of the guinea-pig splenic capsule. 2. In this preparation, noradrenaline (NA), adrenaline (Adr) and alpha-methyl-NA were full agonists, while phenylephrine, dopamine and the catechol-imidazolidine (3,4-dihydroxyphenylamino)-2-imidazolidine, (DPI) were partial agonists. 3. The imidazolidines clonidine and oxymetazoline showed no agonist activity, but both inhibited the agonist activity of NA. pA2 values calculated from Arunlakshana and Schild plots were 6.88 and 6.95 for clonidine and oxymetazoline respectively. Slopes of the Schild plots were close to unity, indicating competitive antagonism. 4. The alpha-adrenoreceptor antagonists phentolamine, prazosin and yohimbine also inhibited the agonist activity of NA with man pA2 values of 8.32, 9.22 and 6.90 respectively. Slopes of Schild plots were significantly less than 1, suggesting that the inhibition was not truly competitive in nature. 5. The irreversible alpha-adrenoreceptor antagonist phenoxybenzamine at low concentrations (10(-9)M) shifted the log concentration-response curve to NA to the right and greatly reduced the maximum response. 6. It is suggested that the adrenoreceptors in the guinea-pig splenic capsule are probably of the alpha 1-type, and that this tissue possesses relatively few spare receptors.

Adrenergic alpha-Agonists↗
PubMed1981

Effect of delay-interval stimuli on delayed symbolic matching to sample in the pigeon.

In Experiment 1, food-deprived pigeons received delayed symbolic matching to sample training in a darkened Skinner box. Trials began with the illumination of the grain feeder lamp (no food sample), or illumination of this lamp, accompanied by the raising of the feeder tray (food sample). After a delay of a few seconds, the two side response keys were illuminated, one with red and one with green light, with positions counterbalanced over trials. Pecking the red (green) comparison produced grain reinforcement if the trial had started with food (no food); pecking red after a no-food sample or green after a food sample was not reinforced. Once matching performance was stable, four stimuli were presented during the delay interval, and their effects on matching accuracy were evaluated. Both illumination of the houselight and the center key with white geometric forms decreased matching accuracy, whereas presentation of a tone and vibration of the test chamber did not. In Experiment 2, pecking the red center key was reinforced with food according to a variable interval schedule. The effects of occasional brief presentations of the four stimuli used in the first experiment on ongoing pecking were assessed. The houselight and form disturbed key pecking, but the tone and vibration did not. Thus, stimuli that interfered with delayed matching also interfered with simple operant behavior. Implications of these results for theories of remembering are discussed.

Journal Article↗
PubMed1981

The diagnosis of hymenoptera hypersensitivity.

Venom skin testing was performed in 216 patients with histories of systemic or local reactions following insect stings. Seventy-six percent of the patients with histories of systemic reactions and 77% of the patients with histories of local reactions had positive skin tests up to 1 mcg/ml. The majority of vespid sensitive patients had positive skin tests to all the vespid species. Significant (p less than .001) cross-reactivity is suggested by regression analysis. This study confirms the value and safety of venom skin testing in hymenoptera hypersensitivity. The implications for venom immunotherapy of the findings are also discussed.

Adult↗
PubMed1980

Displacement of [3H]clonidine binding by clonidine analogues in membranes from rat cerebral cortex.

[3H]Clonidine binds to membranes prepared from rat cerebral cortex by a high affinity saturable process. Using [3H]clonidine of specific activity 5.29 Ci/mmol the Kd for the binding was 1.7 +/- 0.1 nM and the Bmax 9.4 +/- 0.6 pmol/g (n = 5). The Hill coefficient for [3H]clonidine binding to rat cerebral cortex membranes was 0.97 +/- 0.05 (r > 0.93; n = 5) indicating an absence of +ve or -ve cooperativity. The clonidine metabolites 4-hydroxyclonidine; N(2,6-dichlorophenyl)guanidine; N(2,6-dichloro-4-hydroxyphenyl)guanidine; and 2-(2,6-dichlorophenyl)iminoimidazolidine-4-one and the metabolic intermediate 2-(2,6-dichlorophenylamino)imidazole were less effective displacers of [3H]clonidine binding than the parent compound. The first three compounds were more polar and the last two less polar than clonidine as judged by their apparent partition coefficients in octanol/phosphate buffer. Seven imidazolidine derivatives with known alpha-adrenoceptor activity were potent displacers of [3H]clonidine binding: the order of potency being 14,304-18 > naphazoline > clonidine > lofexidine and tiamenidine > CP18,534 > ST600 > ST91. Five 'clonidine-like' drugs displaced [3H]clonidine binding with an order of potency guanabenz > Baya 6781 > guanfacine > clonidine > xylazine >> FLA136. Apparent partition coefficients of the displacing agents have been measured in octanol/phosphate buffer and the importance of this factor is discussed with reference to their in vivo antihypertensive potency and potency as displacers of [3H]-clonidine binding.

Animals↗
PubMed1980

[3H]-Clonidine binding to alpha-adrenoceptors in membranes prepared from regions of guinea-pig kidney: alteration by monovalent and divalent cations.

1 [(3)H]-clonidine binds reversibly to membranes prepared from regions of guinea-pig kidney.2 Higher levels of binding were obtained in the membranes prepared from renal cortex (2.15 +/- 0.27 pmol/g wet wt.) than renal medulla (0.53 +/- 0.07 pmol/g wet wt.) or papilla (0.14 +/- 0.06 pmol/g wet wt.; n = 4).3 Scatchard analysis performed by addition of unlabelled clonidine (1 to 30 pmol) gave figures for the dissociation constant (K(d)) for the binding of [(3)H]-clonidine to renal cortical membranes of 9.0 +/- 0.8 nM and B(max) of 21.6 +/- 1.7 pmol/g wet wt. (n = 4). Hill plots of these data gave gradients close to unity, indicating a lack of co-operative site interactions.4 The monovalent cations, sodium and potassium, and the divalent cation, calcium, produced concentration-dependent decreases in [(3)H]-clonidine binding to membranes prepared from renal cortex, the EC(50)s being respectively 25 mM, 37 mM and 23 mM.5 At low concentrations the divalent cations, magnesium (1 mM) and manganese (0.1 mM), produced enhancement of [(3)H]-clonidine binding. At higher concentrations (>10 mM) both divalent cations inhibited binding.6 Scatchard analysis of [(3)H]-clonidine binding performed in the presence of sodium (100 mM), magnesium (1 mM) or manganese (0.1 mM) revealed that the alterations in binding are primarily due to changes in apparent affinity rather than a change in the number of binding sites. Sodium (100 mM) produced a change in the K(d) from 7.0 +/- 0.4 nM (n = 8) to 42.3 +/- 27.5 nM (n = 3), whereas magnesium (1 mM) decreased the K(d) to 6.0 +/- 0.9 nM and manganese (0.1 mM) to 4.0 +/- 1.0 nM (n = 3).7 The results indicate that [(3)H]-clonidine labels a binding site that has properties resembling an alpha(2)-adrenoceptor, located in the renal cortex. The changes produced by the addition of monovalent and divalent cations are entirely due to changes in the apparent affinity of [(3)H]-clonidine binding.

Animals↗
PubMed1980

Characterization of alpha-adrenoceptors in rat and guinea pig tissues using radiolabeled agonists and antagonists.

Tritium-labeled preparations of the selective alpha 2-adrenoceptor agonist, clonidine, and the selective alpha 1-adrenoceptor antagonists, prazosin and WB 4101, were examined for their suitability as ligands for receptor assay. In the rat brain, 3H-clonidine bound specifically with high affinity to membrane sites, and drug displacement studies indicated that these were alpha 2-adrenoceptors. The structural requirements for this receptor were defined by examining a range of clonidine analogues. 3H-Clonidine binding to peripheral tissues of the rat was very low, although peripheral tissues from guinea pig exhibited higher binding. Specific 3H-clinidine binding was not reduced after chemical sympathectomy, suggesting that the binding site, although having characteristics of an alpha 2-adrenoceptor, was not located presynaptically. Studies with 3H-WB 4101 in rat cerebral cortex indicated that this ligand bound to an alpha 1-adrenoceptor which was independent of the 3H-clonidine-binding site. 3H-Prazosin was a ligand for alpha 1-adrenoceptors in guinea pig brain and also in membranes from seminal vesicle. However, in the latter tissue, characterization of the binding site was hampered by a high degree of nonspecific binding (50% of total binding).

Animals↗
PubMed1979

The characteristics of [3H]-clonidine binding to an alpha-adrenoceptor in membranes from guinea-pig kidney.

1. [3H]-clonidine binds to membranes prepared from guinea-pig kidney. 2. At 25 degrees C the binding is rapid and saturable. 3. Scatchard analysis of the binding data showed that the Kd for [3H]-clonidine binding in kidney membranes is 8.54 nM and the density of binding sites 12.5 pmol/g wet wt. tissue. 4. Hill plots of the binding data showed that there were no cooperative site interactions associated with binding. 5. [3H]-clonidine binding could be displaced by drugs, the most potent being drugs with a high affinity for the alpha-adrenoceptor. The neuroleptic drugs (+)-butaclamol, cis-clopenthixol and cis-flupenthixol at high concentration also displaced [3H]-clonidine binding. 6. Drugs acting as agonists or antagonists of beta-adrenoceptors, histamine receptors, acetylcholine receptors as well as prostaglandins E1, E2, F1alpha and F2alpha, angiotensin II, arginine vasopressin, naloxone, nalorphine and pargyline had little effect on binding. 7. It is likely that the binding site labelled by [3H]-clonidine in guinea-pig kidney membranes is an alpha-adrenoceptor similar in some pharmacological aspects to an alpha2-adrenoceptor.

Animals↗