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Biomedical subjects

J R Peters

Publications and source records attributed to J R Peters.

125 records · Page 7Linked to original sources
PubMed1980

Oestrogen and progesterone change the binding characteristics of alpha-adrenergic and serotonin receptors on rabbit platelets.

The binding characteristics of the alpha-adrenergic and serotonin receptors on intact rabbit platelets were identified using [3H]-dihydroergocryptine and [3H]-5-hydroxytryptamine respectively. In untreated female rabbits a single slpha-adrenoceptor and two serotonin receptors were identified with ligand affinities similar to those in human platelets. The effects of oestrogen and/or progesterone on the alpha-adrenergic and serotonin receptors of rabbit platelets were studied. Oestrogen alone increased the capacity of serotonin receptors but reduced that of the alpha-adrenoceptor. Oestrogen plus progesterone reduced the capacity of both receptors and reduced the affinity of the alpha-adrenoceptor. The possible mechanisms of the steroid-induced changes and the implications of these with regard to the effects of the oral contraceptive pill are discussed.

Animals↗
PubMed1980

Relationship of guanabenz concentrations in brain and plasma to antihypertensive effect in the spontaneously hypertensive rat.

The antihypertensive agent guanabenz (E-2,6-dichlorobenzylidene aminoguanidine acetate. Wy-8678) was administered i.v. in single doses of 10, 32 and 100 microgram/kg to groups of spontaneously hypertensive rats. Mean arterial blood pressure and heart rate were monitored continuously. Animals were decapitated at predetermined time intervals and concentrations of the drug in whole brain and plasma were measured by a specific gas chromatographic method. After an initial transient increase in blood pressure, significant dose-dependent maximal decreases in pressure of 15 +/- 8, 46 +/- 20 and 59 +/- 15 mm Hg (mean +/- S.D.) were observed 15 to 30 min after injection of the above respective doses. At the line of the maximal decreases in pressure (T delta max), concentrations of guanabenz in brain were 10 +/- 2, 29 +/- 8 and 89 +/- 21 ng/g and correlated significantly with dose and the magnitude of blood pressure change. The correlation between concentration in brain and change in blood pressure was also significant at subsequent sacrifice times. Concentrations of guanabenz in plasma were below the limit of detection after the 10 microgram/kg dose. At the two higher doses, concentrations in plasma were dose related but did not correlate with decreases in blood pressure. The correlation between concentration in brain and change in blood pressure is in agreement with the predominantly central mechanism of action of guanabenz.

Animals↗
PubMed1979

Effect of oral contraceptives on platelet noradrenaline and5-hydroxytryptamine receptors and aggregation.

Characteristics of receptor sites on platelets for noradrenaline (NA) and serotonin (5-HT) changed significantly between day 21 and day 28 of treatment in healthy women taking oral contraceptives. NA-induced and 5-HT-induced platelet aggregation and 5-HT uptake vaired accordingly. In untreated women with normal cycles no changes in either receptor site or in platelet function occurred between the luteal and postmenstrual phases. It is concluded that the observed changes are due to a pharmacological effect of the oral contraceptive rather than a normal physiological variation.

Adult↗
PubMed1977

Thermodynamics of binding to native alpha-chymotrypsin and to forms of alpha-chymotrypsin in which catalytically essential residues are modified; a study of "productive" and "nonproductive" associations.

The standard free energy (deltaG degrees), enthalpy (deltaH degrees), and entropy (deltaS degrees) of association for proflavin and D- and L-N-AcTrp have been obtained at pH 7.8 for native alpha-chymotrypsin (Cht) and for forms of Cht in which essential catalytic residues of the active site are modified. The modified Cht forms studied are dehydroalaninyl-195-alpha-Cht and N-methylhistidinyl-57-alpha-Cht. Associations to native Cht (pH 7.8) are characterized by negative deltaH degrees and deltaS degrees values (i.e., for L-AcTrp deltaH degrees = -9.1 kcal/mol and deltaS degrees = -21 eu at T = 25 degreesC). In contrast, we found associations to modified Chts to be characterized by an enthalpy near zero and a positive entropy of association, the values of the deltaH degrees and deltaS degrees for association to the modified Cht forms being similar to those expected for transfer of small aromatic molecules from water to a nonpolar solvent phase. Differences in deltaH degrees and deltaS degrees observed for binding of substrate analogues and inhibitors to modified and native Cht (pH 7.8) are approximately + 10 kcal/mol and +30 eu, respectively. Data from D. D. F. Shiao ((1970), Biochemistry 9, 1083) similarly show differences of comparable magnitude between binding of substrate analogues to active alpha-Cht (pH 7.8) and the His-57 protonated form of alpha-Cht (pH 5.6). The negative deltaH degrees and deltaS degrees values of associations for binding to active alpha-Cht indicate that a substrate-induced conformational change occurs on substrate association with the primary binding site (S1), which does not occur in Ser-195 and His-57 modified Cht. From these differences we infer a linkage between binding of substrate into S1 and the catalytic residues in the nucleophilic subsite (S1-S1'). Our data also show that associations of substrate analogues into potentially productive Michaelis complexes S1 cannot be easily differentiated from associations that are nonproductive (i.e., nonactivated) from their deltaG degrees obsd, but may be differentiated by their respective deltaH degrees obsd and deltaS degrees obsd for association. Accordingly, it is indicated that the probable substrate association-activation process, characterized thermodynamically in this work, occurs in the substrate binding step and leads to lowered free energies of activation in catalytic steps succeeding binding however, the process does not influence the observed strength of substrate binding.

Binding Sites↗
PubMed1976

Tricyclic antidepressants and cardiac conduction: changes in ventricular automaticity.

Ventricular dysrhythmias result from changes in the automaticity or the conduction properties of the specialized conduction system. Tricyclic antidepressants have been reported to cause ventricular dysrhythmias in humans and experimental animals. Consequently, it seemed to interest to determine whether these substances influence ventricular automaticity. Ventricular rhythm was produced in anesthetized dogs by blocking atrioventricular conduction. Low doses of imipramine, amitriptyline and nortriptyline resulted in small but significant increases in automaticity. Relatively high doses of these agents suppressed automaticity markedly. These changes could play a role in the development of dysrhythmias.

Amitriptyline↗
PubMedDate not supplied

Suppression of ventricular automaticity by antidysrhythmic agents.

In view of the potentially important role of automaticity in the genesis of ventricular dysrhythmias, the effects of four widely used antidysrhythmic agents on ventricular automaticity were examined in anesthetized dogs at doses previously shown to antagonize experiments induced rhythm disturbances. Quinidine, and particularly procainamide, lidocaine and propranolol slowed ventricular rate in A-V blocked dogs. Quinidine and procainamide but particularly the last two agents also markedly prolonged overdrive suppression. Thus, all four substances depressed automaticity. However, propranolol was effective at doses substantially lower than those required to antagonize several experimental dysrhythmias.

Animals↗
PubMedDate not supplied

Longitudinal evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy: effects of angiotensin-converting enzyme inhibition.

A prospective self-controlled evaluation of renal function in non-insulin-dependent diabetic patients with early nephropathy, mild to moderate hypertension, and retinopathy was undertaken over a 1-year period. Thereafter, the effects of treatment with captopril on blood pressure, albumin excretion, and renal function were assessed. Glomerular filtration rate (GFR), effective renal plasma flow (ERPF), and systolic and diastolic blood pressures remained stable during the pretreatment period; 24-h urinary protein excretion increased progressively from 0.79 +/- 0.13 to 1.23 +/- 0.18 g/24 h (p < 0.05) (mean +/- standard error). Captopril (25 mg b.i.d.) for 3 months reduced systolic and diastolic blood pressures significantly (p < 0.01). Simultaneously, 24-h urinary protein excretion declined by 41 +/- 2.4%, to 0.70 +/- 0.12 g/24 h (p < 0.05) while GFR, ERPF, and fractional filtration demonstrated small but insignificant changes. Subsequently, increase in captopril to 50 mg b.i.d. for the remaining 6 months did not produce further significant changes in renal hemodynamics, blood pressure, or urinary protein excretion (0.48 +/- 0.10 g/24 h at the termination of the study). Non-insulin-dependent diabetic patients with early nephropathy and mild to moderate hypertension demonstrate a progressive increase in urinary protein excretion. Administration of captopril resulted in prompt control of hypertension and reversal of the increase in urinary protein excretion.

Adult↗
PubMedDate not supplied

Modulation of glucose and growth hormone responses to meals and exercise in type 1 diabetes by cholinergic muscarinic blockade.

Anticholinergic drugs suppress nocturnal and exercise-related growth hormone (GH) secretion in Type 1 diabetes; nocturnal GH suppression is associated with a fall in fasting plasma glucose levels. The aim of this study was to assess the effect of GH suppression on glucose levels following a period of meals and exercise in physiological pattern. Six Type 1 diabetic men recruited from the outpatient clinic were studied in random order at least 1 week apart. After an overnight fast subjects received two-thirds of their usual subcutaneous insulin and either 200 mg oral pirenzepine or placebo at time 0 min. Between 90 and 120 min subjects exercised continuously on an ergometric cycle. Standard meals or snacks were eaten at 30, 150, 270, and 390 min. Venous blood was collected from an indwelling cannula between 0 and 570 min. The mean incremental rise in plasma glucose after breakfast (delta peak/90 min) was 2.6 +/- 0.5 (mean +/- SEM mmol l-1 (pirenzepine) vs 4.5 +/- 0.8 (placebo)), p < 0.05. Following exercise the fall in plasma glucose (delta gluc90-240 min) was 6.4 +/- 1.9 (pirenzepine) vs 2.0 +/- 1.3 (placebo), p < 0.005. The exercise-related peak rise in GH was 12.6 +/- 3.3 (pirenzepine) vs 28.5 +/- 6.0 mU l-1 (placebo), p = 0.08. Excluding one outlying result there was an inverse correlation between the integrated exercise-related increase in GH between 90 and 240 min and the fall in glucose over the corresponding time period (n = 11, r = -0.75, p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Early-morning hyperglycemia in IDDM. Acute effects of cholinergic blockade.

Growth hormone (GH) hypersecretion in insulin-dependent diabetes mellitus (IDDM) subjects has been shown to be causally related to early-morning hyperglycemia. We studied the effect of nocturnal GH suppression on acute glycemic control in six IDDM patients during a constant overnight insulin infusion (0.075 mU.kg-1.min-1). In control experiments (infusion of insulin alone), plasma glucose increased from 5.6 +/- 0.6 mM at 2400 to 11.1 +/- 1.3 mM at 0900 (P = .0024). When in addition the cholinergic muscarinic antagonist pirenzepine was given (100 mg at 2200 and again at 2400), plasma glucose increased from 5.6 +/- 0.3 mM at 2400 to 8.4 +/- 1.4 mM at 0900 (P greater than .05). The nocturnal surges of GH that were demonstrated in all patients during the control nights were suppressed during the treatment nights. There were no significant changes in insulin, cortisol, or epinephrine concentrations. Mean glucagon and norepinephrine concentrations. Mean glucagon and norepinephrine concentrations were reduced from 127 +/- 2.7 ng/L and 8.7 +/- 0.5 nM to 101 +/- 1.9 ng/L (P less than .001) and 3.5 +/- 0.2 nM (P less than .001) on control and treatment nights, respectively. Neither glucagon nor norepinephrine concentrations changed significantly between 2400 and 0900 on either control or treatment nights. We conclude that nocturnal GH suppression by pirenzepine during a constant low-rate insulin infusion is associated with an attenuation of the early-morning plasma glucose rise.

Adult↗