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Biomedical subjects

C R Jones

Publications and source records attributed to C R Jones.

At least 109 records · Page 6Linked to original sources
PubMed1987

Autoradiographic localization of receptors in the mammalian cardiovascular system.

1. Autoradiographic techniques have been used to examine the location of beta-adrenoceptors in the heart and beta-adrenoceptors, substance P receptors and muscarinic cholinoceptors in blood vessels. 2. Both beta 1-adrenoceptors and beta 2-adrenoceptors were present in guinea-pig and human heart, on the myocardium and associated with the cardiac nerves and blood vessels. 3. Nerves on the vasculature and vascular smooth muscle contained beta-adrenoceptors and muscarinic cholinoceptors. 4. Receptors for substance P and beta-adrenoceptors, but not muscarinic cholinoceptors were present on endothelial cells.

Animals↗
PubMed1987

Characterization and autoradiographic localization of beta-adrenoceptor subtypes in human cardiac tissues.

1 Receptor autoradiography using (-)-[125I]-cyanopindolol (CYP) was used to study the distribution of beta-adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium. 2 The binding of (-)-[125I]-CYP to slide-mounted tissue sections of human right atrial appendage was time-dependent (K1 = 4.11 +/- 1.01 X 10(8) M-1 min-1, K-1 = 1.47 +/- 0.25 X 10(-3) min-1, n = 3), saturable (42.02 +/- 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (-):8.97 +/- 0.02, (+):6.88 +/- 0.06, n = 3). 3 The proportions of beta-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34-45%) of the beta-adrenoceptors were of the beta 2-subtype. 4 Images from X-ray film and nuclear emulsion coated coverslips exposed to (-)-[125I]-CYP-labelled sections showed an even distribution of beta-adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly beta 2-adrenoceptors. beta 2-Adrenoceptors were localized to the intimal surface of coronary arteries. 5 The selective beta 1-adrenoceptor agonist RO363 and beta 2-selective agonist procaterol produced concentration-dependent inotropic responses in right atrial appendage strips. Responses to RO363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with beta 1-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at beta 2-adrenoceptors. 6 The finding that a significant proportion of human myocardial adrenoceptors are of the beta 2-subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.

Adolescent↗
PubMed1986

Changes in rabbit platelet alpha and beta adrenoceptor number and platelet aggregation.

Treatment with phenoxybenzamine caused a decrease in the number of alpha but not beta adrenoceptor ligand binding sites on platelets from male rabbits and thus a decrease in the ratio of alpha/beta adrenoceptor number. This was accompanied by decreased aggregation both in the presence and absence of propranolol. In contrast in female rabbits maturation and oestrogen treatment resulted in a decrease in both alpha and beta adrenoceptor ligand binding and no change in the alpha/beta adrenoceptor ratio or in the aggregatory response of the platelets to adrenaline in the absence of propranolol.

Animals↗
PubMed1986

Desensitization of platelet alpha 2-adrenoceptors after short term infusions of adrenoceptor agonist in man.

The effect of intravenous infusion of catecholamines and related drugs on human platelet alpha 2-adrenoceptor number and function was investigated. Short (60-120 min) infusions of catecholamines with alpha 2 agonist activity in vivo produced attenuation of the platelet responses to adrenaline in vitro. This desensitization was specific for the adrenaline induced aggregatory response. The maximum number of [3H]yohimbine binding sites on platelets was not altered by adrenaline infusion. The ability of adrenaline to reduce platelet cyclic AMP levels was significantly reduced after the infusions. Acute infusions of alpha 2-adrenoceptor agonists may alter the coupling of the platelet alpha 2-adrenoceptor to adenylate cyclase.

Adolescent↗
PubMed1986

Studies on alpha 2-adrenoceptors in rabbits with perinephritis hypertension.

Increased responses to intravenous injections of the full alpha 2-adrenoceptor agonists, alpha-methyl noradrenaline and noradrenaline, were observed in conscious rabbits with perinephritis hypertension. However, responses to the partial agonist, BHT 920, and the antagonist, idazoxan, were unchanged. These increased responses to noradrenaline and alpha-methyl noradrenaline did not appear to be related to the alpha 1- or beta-adrenoceptor activity or to altered clearance of the agonists. The pro-aggregatory response of platelets from hypertensive rabbits and normotensive rabbits to adenosine diphosphate (ADP) was similar, but the sensitivity of platelets from hypertensive rabbits to the adrenaline potentiation of the pro-aggregatory response was increased. This was not related to changes in the number of alpha 2-adrenoceptor binding sites or to changes at platelet beta-adrenoceptors. In contrast the aggregatory responses to the partial agonist, guanabenz, were similar in normotensive and hypertensive animals. In rabbits with perinephritis hypertension responses to phenylethanolamines (full agonists at the alpha 2-adrenoceptor) were increased in vivo in the conscious animal and in vitro in platelets, whereas responses to imidazolines which are partial agonists were similar in normotensive and hypertensive animals. These differences may be related to alterations in the coupling of alpha2-adrenoceptor activation to response in the hypertensive rabbits.

Adrenergic alpha-Agonists↗
PubMed1986

Intracoronary thrombolytic therapy performed within a coronary care unit: one year's experience.

Acute myocardial infarction is associated with a high incidence of occluding coronary arterial thrombi. Thrombolytic therapy has been advocated to restore coronary artery blood flow and to reduce myocardial damage. Coronary arteriography and intracoronary thrombolytic therapy was administered to 61 patients admitted to a Coronary Care Unit within eight hours of symptoms. Successful reperfusion was obtained in 38 of 46 single vessel occlusions associated with a first coronary attack. Failure of reperfusion occurred in patients with two vessel occlusions or with cardiogenic shock. This study demonstrates the feasibility of applying this technique within a Coronary Care Unit with low capital and running costs, and suggests that its widespread application is possible even within the setting of a District General Hospital.

Coronary Angiography↗
PubMed1985

A comparison of alpha 2-adrenoceptor regulation in brain and platelets.

Functional responses and alpha 2-adrenoceptor radioligand binding were studied in brain and platelets of rabbits under a variety of circumstances. The effects of oestrogen treatment and maturation were studied in female rabbits and of aging and amitriptyline treatment in male rabbits. No correlation was found between changes in brain and platelets either in response or alpha 2-adrenoceptor ligand binding under any of the conditions examined.

Aging↗
PubMed1985

The effects of sexual maturation on alpha-adrenoceptors in female rabbits.

alpha-Adrenoceptor number and function were examined in brain, platelets, and other peripheral tissues of young (2-3 months) and mature (6-8 months) non pregnant female rabbits. alpha1-Adrenoceptor number was significantly higher in forebrain, hindbrain, spleen and heart of mature rabbits. alpha2-Adrenoceptor number, on the other hand, was found to be significantly lower in platelets, forebrain and spleen but not changed in hindbrain and kidney of mature animals compared to young females. There was a significant reduction in platelet aggregation with maturation. However, no change in in vivo pressor or depressor responses to alpha-adrenoceptor agonists was observed in vivo.

Adrenergic alpha-Agonists↗
PubMed1985

Maternal and fetal platelet responses and adrenoceptor binding characteristics.

Paired blood samples were obtained from mothers (venous) and babies (cord venous blood) at the time of delivery by caesarean section under epidural anaesthetic. Fetal platelets failed to aggregate in response to adrenaline in vitro although adrenaline could potentiate the threshold response to adenosine diphosphate (1 microM). Fetal platelet responses to collagen and 8 Arg vasopressin did not differ significantly from maternal responses. Maternal and fetal platelets also showed similar inhibition of aggregation after activation of adenylate cyclase (PGE1 and parathormone), in contrast to the inhibition of adenylate cyclase by adrenaline. Alpha 2 adrenoceptors were investigated using [3H] yohimbine binding receptor number and were reduced modestly but significantly on fetal compared to maternal platelets. The failure of fetal platelet aggregation in response to adrenaline appears to be related to a failure of receptor coupling and may represent a delayed maturation of fetal platelet alpha receptors or a response to increased circulating catecholamines during birth.

Adenosine Diphosphate↗
PubMed1985

alpha-Adrenoceptor regulation in vivo and in vitro in the rabbit.

The relationship between alpha-adrenoceptor number and response has been studied in rabbits under a range of physiological and pathological conditions. The effects of irreversible alpha-adrenoceptor blockade, maturation, ageing, oestrogen treatment, adrenaline infusion, perinephritis hypertension and sinoaortic denervation on alpha-adrenoceptor number and response were examined. alpha-Adrenoceptor number was measured by radioligand binding. [3H]Prazosin and [3H]clonidine were used as ligands to measure alpha 1- and alpha 2-adrenoceptor number in spleen and [3H]yohimbine to measure alpha 2-adrenoceptor number on platelets. Responses in vivo were studied by examining the pressor responses to a range of alpha-adrenoceptor agonists. The functional response of platelets was examined in vitro by using the aggregatory response to adrenaline. Reductions in alpha 2-adrenoceptor ligand binding were consistently accompanied by equivalent reductions in alpha 2-adrenoceptor-mediated responses. In contrast large reductions in [3H]prazosin binding were observed with little or no change in alpha 1-adrenoceptor-mediated responses. These results would be consistent with a large receptor reserve for alpha 1-adrenoceptors but few if any spare alpha 2-adrenoceptors in the vasculature or on platelets. Increased responses to both alpha 1- and alpha 2-adrenoceptor agonists were observed in animals with sinoaortic denervation and to alpha 1-adrenoceptor agonists in rabbits with perinephritis hypertension. These increases in response were not accompanied by increases in radioligand binding and may be related to alterations in the coupling of receptor activation to end-organ response.

Adrenergic alpha-Agonists↗
PubMed1985

Acute and chronic regulation of alpha 2-adrenoceptor number and function in man.

Agonist regulation of platelet alpha 2-adrenoceptors was examined in human volunteers after acute elevations of adrenoceptor agonist and during chronic elevation of plasma catecholamines in two patients with phaeochromocytoma. Platelet alpha 2-adrenoceptor number was measured by radioligand binding [( 3H]yohimbine) and alpha 2-adrenoceptor function measured by turbidimetric platelet aggregation. Short term infusion of adrenoceptor agonists with alpha 2 activity caused reductions in the platelet response to adrenaline in vitro; conversely an increase in activity was observed postoperatively in two patients after removal of phaeochromocytoma. The changes in platelet response were not accompanied by changes in alpha 2-adrenoceptor number. It is proposed that a process of receptor inactivation occurs during desensitization and this is responsible for the dynamic regulation of platelet responses.

Adolescent↗
PubMed1985

Alpha-adrenoceptor changes after oestrogen treatment in platelets and other tissues in female rabbits.

alpha 2-Adrenoceptors on blood platelets have been widely used as a model for alpha-adrenoceptors in less accessible tissues. The effect of oestrogen (200 micrograms/day intramuscularly) on alpha 2-adrenoceptor number and function was studied in immature female rabbits. alpha 2-adrenoceptor number was measured in whole platelets, and membrane preparations of forebrain, hindbrain, spleen and kidney by radioligand binding. alpha 2-Adrenoceptor function was examined by measuring platelet aggregation in vitro and circulatory responses to selective alpha 2-adrenoceptor agonists in vivo. Oestrogen treatment resulted in a significant decrease in platelet alpha 2-adrenoceptor number and function. However, no changes were observed either in receptor number in other tissues or in responses to alpha 2-agonists in vivo. The results suggest that oestrogen modulation of rabbit platelet alpha 2-adrenoreceptor number and function may be different from that of brain, kidney and spleen. Caution should be exercised in extrapolating results from platelets to alpha-adrenoceptors at other sites.

Animals↗
PubMed1985

Effects of verapamil and nisoldipine on human platelets: in vivo and in vitro studies.

Inhibition of platelet aggregation was observed after 4 days of oral dosing with the calcium antagonists, verapamil (160 mg) or nisoldipine (20 mg) but not following acute dosing. These effects were observed at plasma concentrations that had no effect on platelet aggregation when investigated in vitro. Verapamil added in vitro inhibited adrenaline-induced platelet aggregation at relatively low concentrations (IC50 16 microM) but only inhibited aggregation to adenosine diphosphate at very high concentrations (IC50 700 microM). Nisoldipine, a dihydropyridine, added in vitro had no effect on platelet aggregation induced by adenosine diphosphate but inhibited by 67%, the secondary phase of platelet aggregation induced by adrenaline. Verapamil but not nisoldipine displaced [3H]-yohimbine from the specific binding sites on human platelets, suggesting an interaction with alpha 2-adrenoceptors. Inhibition of adrenaline-induced aggregation by verapamil in vitro may be a result of antagonism of alpha 2-adrenoceptors but long term treatment with both verapamil and nisoldipine also inhibits platelet aggregation mechanisms other than by alpha 2-adrenoceptor blockade.

Adult↗
PubMed1985

Plasma catecholamines and modes of delivery: the relation between catecholamine levels and in-vitro platelet aggregation and adrenoreceptor radioligand binding characteristics.

Catecholamines were measured in maternal venous, and mixed umbilical cord blood. Maternal catecholamines were significantly (P less than 0.01) reduced by epidural analgesia with a 36% reduction in noradrenaline and a 33% reduction in adrenaline. Fetal catecholamines were elevated at birth with a 3-8 fold increase in noradrenaline but not adrenaline during spontaneous vaginal delivery. The lowest fetal catecholamines were obtained in the group delivered under epidural analgesia; lower plasma catecholamines were not associated with adverse respiratory effects. Fetal platelets showed impaired alpha 2-adrenoceptor function with absent aggregatory responses to adrenaline in vitro. The defect in platelet function was unlikely to be related to changes in the number of fetal platelet alpha-receptors or to changes in receptor affinity for adrenaline, as fetal platelets failed to aggregate to adrenaline from deliveries with high and low cord blood catecholamines.

Adult↗
PubMed1985

Electrophysiological effects of felodipine in combination with metoprolol.

The combined use of some beta-adrenoceptor blocking agents with calcium channel blockers may cause adverse pharmacodynamic drug interactions: hypotension, heart block or even asystole may be precipitated. The electrophysiological effects of combined administration of intravenous metoprolol 10mg and the vasodilating calcium antagonist felodipine (0.1 mg/kg/bodyweight) were assessed in an open study by invasive methods. Following metoprolol, the heart rate was reduced from 69 +/- 24 to 60 +/- 16 beats/min (mean +/- SD, p less than 0.05) with a minor prolongation of the sinus node recovery time. The A-H interval was increased from 94 +/- 25 to 109 +/- 16 msec (p less than 0.005) and the H-V interval was unchanged. The effective refractory period of the atrioventricular node was prolonged from 327 +/- 54 to 361 +/- 62 msec (p less than 0.01) with a minor prolongation of the effective refractory period of the ventricular Purkinje fibres. Systolic and diastolic blood pressures showed a mean reduction of 11 (p less than 0.001) and 6mm Hg (p less than 0.05), respectively. Following felodipine, the changes in heart rate and effective refractory periods of the atrioventricular node and ventricular Purkinje fibres returned towards control values. No further prolongation of the A-H interval resulted and further blood pressure changes were minor. The absence of adverse haemodynamic or electrophysiological effects suggests that this combination of agents may be safely used.

Adult↗
PubMed1985

Alpha-adrenoceptor number and function in platelets from treated and untreated patients with essential hypertension and age- and sex-matched controls.

Alpha 2-receptor number was measured on platelets from 19 healthy normotensive volunteers and 19 patients with essential hypertension, using [3H]-yohimbine binding. Platelet function was assessed using the primary aggregation response to adrenaline. The mean alpha 2-receptor number (Bmax fmol/10(8) platelets) in platelets from normotensive controls was 31 (188 sites/cell) and was significantly higher than in age- and sex-matched hypertensive subjects, for whom Bmax = 24 (144 sites/cell) (P < 0.01 by paired t-test). There was no change in the affinity for [3H]-yohimbine binding. Platelet aggregation responses to adrenaline did not differ between hypertensive and normotensive subjects. Blood pressure reduction with prazosin in eight hypertensive subjects did not alter receptor number either acutely or following 1 month of treatment. These findings may be interpreted as evidence for enhanced receptor coupling to functional responses of a significantly smaller receptor population in patients with essential hypertension.

Adult↗