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Biomedical subjects

M Schachter

Publications and source records attributed to M Schachter.

At least 145 records · Page 8Linked to original sources
PubMed1989

Human vascular responses to endothelin-1: observations in vivo and in vitro.

These studies have investigated the effect of endothelin-1 (ET-1) on human resistance vasculature in vivo and in vitro. ET-1 was infused via the brachial artery and forearm blood flow (FBF) measured by venous occlusion plethysmography. Isolated resistance vessels were studied in a myograph. ET-1 (10 pmol-10 nmol/min, i.a.) reduced forearm blood flow. Endothelin-1-induced forearm vasoconstriction was slow to recover following washout. ET-1 (10 pM-10 nM) contracted isolated human subcutaneous and omental resistance vessels. Contractile responses to ET-1 were sustained and washout recovery was slow. Responses to ET-1 displayed marked tachyphylaxis. Calcium channel blockers and removal of extracellular calcium failed to completely abolish responses to ET-1 in vitro.

Adult↗
PubMed1988

The effect of a bradykinin antagonist on vasodilator responses with particular reference to the submandibular gland of the cat.

A bradykinin analogue, D-Arg[Hyp3, Thi5,8, D-Phe7]-Bk, antagonized the vasodilator effect of bradykinin injected close-arterially in the submandibular salivary gland of the cat, without affecting that due to acetylcholine or nerve stimulation. The same analogue also antagonized the hypotensive response to bradykinin injected intravenously in cats and rabbits. We conclude that functional hyperaemia in the submandibular gland of the cat is not due to the release of bradykinin by salivary kallikrein.

Animals↗
PubMed1988

Low-density lipoproteins increase intracellular calcium in aequorin-loaded platelets.

Low-density lipoproteins activate isolated human platelets. The mechanism of this activation is unknown, but may involve increased phosphoinositide turnover. We have examined the effect of low-density lipoproteins on intracellular calcium concentrations in platelets loaded with the photoprotein aequorin. The lipoproteins induced concentration-dependent increases in intracellular calcium, associated with shape change and aggregation. These responses could be partially inhibited by the removal of extracellular calcium and by pre-incubation with acetylsalicylic acid. They were also antagonised by agents which increase cellular concentrations of cyclic adenosine and guanosine monophosphates. It is not clear whether the platelet-lipoprotein interaction involves a 'classical' lipoprotein receptor.

Aequorin↗
PubMed1988

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration.

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.

Antidepressive Agents↗
PubMed1988

Size and site-dependent heterogeneity of human vascular responses in vitro.

Ring segments of splanchnic, peripheral, coronary, pulmonary and uterine conduit arteries obtained during surgery were studied in tissue baths. Resistance arteries dissected from various sites were studied in a myograph. Both conduit and resistance vessels contracted in response to the alpha 1-agonist phenylephrine (10(-7) to 10(-4) mol/l), an effect that was antagonized by the alpha 1-antagonist doxazosin (10(-8) to 10(-6) mol/l). However, the alpha 2-agonists BHT 933 (10(-7) to 10(-4) mol/l) and UK 14304 (10(-7) to 10(-4) mol/l) only contracted the resistance vessels and not the conduit arteries. The response to BHT 933 was competitively antagonized by the alpha 2-antagonist yohimbine (3.10(-8) to 3.10(-7) mol/l) and the magnitude of the contractile response was inversely related to vessel size. Similarly, neuropeptide Y (10(-9) to 10(-6) mol/l) contracted only the resistance vessels, and induced marked tachyphylaxis. Atrial natriuretic peptide (ANP; 10(-8) to 10(-6) mol/l) produced concentration-dependent relaxation in all conduit arteries studied, being ineffective in resistance arteries from subcutaneous or omental sites, but relaxed those from renal tissue and skeletal muscle. Calcitonin gene-related peptide (10(-8) to 10(-6) mol/l) and vasoactive intestinal peptide (10(-9) to 10(-6) mol/l) relaxed both conduit and resistance arteries. This response was dependent on the integrity of the endothelium in the systemic conduit but not the resistance vessels. These results indicate that the receptors for adrenergic agonists and vasoactive peptides are varyingly distributed throughout the human vasculature.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1987

Calcium transients in human platelets monitored by aequorin, fura-2 and quin-2: effects of protein kinase C activation and inhibition.

Tumour-promoting phorbol esters and 1,2-dioctanoyl-sn-glycerol both induce calcium transients in platelets. However, these can only be detected in platelets loaded with aequorin, but not in those loaded with the fluorescent probes quin-2 and fura-2 presumably because of intracellular calcium buffering. Several effects induced by phorbol esters and diacylglycerols, including the rise in (Ca2+)i, the stimulation of Na+/H+ transporter and the inhibition of the effects of thrombin alone on (Ca2+)i are potently antagonised by staurosporine, a compound known to inhibit protein kinase C. Higher concentrations of staurosporine themselves inhibit the thrombin-induced calcium transient. Staurosporine inhibits the effects of phorbol esters and dioctanoyl glycerol with equal potency although the latter does not cause enzyme translocation of cytosolic protein kinase C to membranes. These results therefore suggest that some, if not all, the effects of protein kinase C activation can occur without translocation of the enzyme.

Aequorin↗
PubMed1987

Autoradiographic localisation of NPY receptors in rabbit kidney: comparison with rat, guinea-pig and human.

In vitro labelling of neuropeptide Y binding sites with 125I-NPY was performed in rabbit kidney sections. Autoradiographic and histochemical techniques localised these binding sites to the proximal convoluted tubules and the vascular smooth muscle. In comparison, 125I-NPY binding was absent from the rat, guinea pig and human kidney. Possible physiological roles for the putative NPY receptors in rabbit renal function are discussed.

Animals↗
PubMed1987

Do calcium antagonists affect platelets?

Inappropriate platelet activation is thought to have a pathophysiological role in several cardiovascular disorders, including ischaemic heart disease and hypertension. Calcium antagonists are increasingly used in the therapy of these diseases. An inhibitory effect on platelet activation would clearly be a useful component of their therapeutic effect. Since a raised intracellular calcium concentration is crucial for platelet activation, and much of the calcium enters from the extracellular medium, such an effect might be anticipated. In fact, calcium antagonists consistently inhibit platelet activation in vitro, and somewhat less consistently ex vivo. However, many unanswered questions remain. Clinically attained drug concentrations in plasma may be too low to be effective, there appear to be no calcium antagonist receptors on the platelet, and the mechanism of action of the drugs is unclear. More importantly, it is not known whether an anti-platelet effect, if it occurs, is of practical rather than theoretical, value to the patient. These problems will need much more investigation.

Blood Platelets↗
PubMed1987

The actions of calcitonin gene related peptide and vasoactive intestinal peptide as vasodilators in man in vivo and in vitro.

1 The two peptides calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) produced marked dilatation of the forearm vascular bed when infused via the brachial artery. 2 CGRP relaxed preconstricted segments of human radial, coronary, gastric and cerebral arteries in an endothelium dependent manner. 3 VIP relaxed human gastric and transverse cervical arteries in an endothelium dependent manner, but relaxation of the human pulmonary artery was not dependent on endothelium. 4 The characteristics of the endothelium dependent relaxation of these medium-sized muscular arteries indicated involvement of the endothelium derived relaxing factor in vitro. 5 Caution is expressed in drawing comparisons between the mechanisms involved in the in vivo and in vitro vascular responses.

Adult↗
PubMed1987

New synthetic antagonists of bradykinin.

1 A new synthetic bradykinin analogue was found to be an antagonist of bradykinin-induced vascular permeability in rabbit skin. It was effective in equimolar concentrations. 2 These analogues also antagonized the action of bradykinin in contracting the guinea-pig isolated ileum. The mean pA2 values of five different antagonists ranged from 5.3-6.4 respectively, on this preparation. 3 Our observations, together with those of others suggest that these antagonists act on the same receptor types, viz., B2, in rabbit blood vessels and in smooth muscle of guinea-pig ileum. 4 Our results support the view that the way is now promising for the synthesis of potent specific antagonists of bradykinin for experimental and therapeutic use.

Animals↗
PubMed1987

Characterization of neuropeptide Y receptors in rabbit kidney: preliminary comparisons with rat and human kidney.

Neuropeptide Y (NPY) is a cotransmitter with noradrenaline in perivascular sympathetic nerves. It constricts some vessels and in others potentiates other vasoconstrictors. NPY produces vasoconstriction and natriuresis in the isolated perfused rat kidney, but induces renal vasoconstriction without natriuresis in the intact rabbit. We have performed radioligand binding studies in rat, rabbit, and human kidney, using 125I-NPY. In rabbit cortex there is a high density of high-affinity binding (Bmax = 560 fmol/mg, Kd = 83 pM). Receptor density in rabbit medulla is approximately 200 fmol/mg, with much higher nonspecific binding. Binding was displaced with high potency by human NPY and peptide YY, weakly by pancreatic polypeptide, and not at all by structurally unrelated peptides. There was no detectable specific binding in rat kidney, and only a very small number of binding sites in human cortex (10 fmol/mg). No specific binding was obtained in human medulla. These results have been confirmed by light microscope autoradiography, which suggests that NPY binding sites in rabbit cortex are localised to the proximal convoluted tubules and vascular smooth muscle. The functional implications of the above species differences remain to be determined.

Animals↗
PubMed1987

Care givers in the workplace: employer support for employees with elderly and chronically disabled dependents.

With increasing demands for dependent care, and more women in the work force, employees may be required to balance work and care giving responsibilities. The New York Business Group on Health survey examines the role of business and industry concerning this issue: employer awareness about problems of employees responsible for the care of elderly or chronically disabled dependent family members, and company programs and policies to deal with employee care giver problems. Findings from this exploratory study of 69 companies in the greater New York area indicate that approximately half are aware of care giver needs, and many have identified employee problems in the workplace (lateness, absenteeism, etc). Few have programs designed specifically for care givers. However, larger companies and those with a predominantly female work force have more policies and programs that can accommodate care giver needs. Various strategies currently being tried by companies to support care givers are described.

Aged↗
PubMed1986

Characterisation of a high-affinity VIP receptor in human lung parenchyma.

A method is described for preparing human lung parenchymal membranes essentially free of carbon contamination. Using this technique, a high-affinity 125I-VIP-binding site has been characterised. The receptor density is approx. 200 fmol/mg protein, and the Kd of 125I-VIP by saturation binding is 200 pM. The dissociation kinetics are complex and cannot be described by first-order kinetics. Several VIP-related peptides displace 125I-VIP from this binding site with a rank order of potency: VIP greater than rat GRF greater than PHM greater than PHI greater than human GRF greater than secretin greater than glucagon. Displacement curves of these peptides exhibited slope factors significantly less than unity with the exception of human GRF.

Animals↗