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Biomedical subjects

L R McMartin

Publications and source records attributed to L R McMartin.

6 recordsLinked to original sources
PubMed1995

Signalling pathways in cardiac failure.

UNLABELLED: 1. Cardiac failure in humans and in animal models is associated with a marked desensitization of the catecholamine signalling pathway. 2. Beta 1- and beta 2- and possibly beta 3-adrenoceptors (beta-AR) are found in the hearts of humans and common laboratory animals such as rats and guinea-pigs. In rats and guinea-pigs chronic stimulation of cardiac beta-AR leads to a rapid loss of beta 2-AR whereas heart failure in humans is associated with a loss of beta 1-AR or beta 1-AR and beta 2-AR. 3. Desensitization is also associated with phosphorylation of beta-AR by beta-AR kinase (beta-ARK) and uncoupling of receptors from the signalling pathway. Beta-ARK but not beta-arrestin activity and mRNA are markedly increased in heart failure. 4. Chronic beta-AR stimulation and heart failure are associated with increases in Gi alpha but little if any change in Gs alpha. 5. The roles of beta gamma subunits of G-proteins, adenylate cyclase subtypes and cAMP dependent protein kinase A in heart failure are unclear at present. ABBREVIATIONS: beta-ARK - beta-adrenoceptor kinase AR - adrenoceptor G-protein - GTP binding protein

Animals↗
PubMed1990

The autoradiographic localization of adenylate cyclase in rat kidney using [3H]forskolin.

The localization of [3H]forskolin binding to microscope slide mounted sections of rat kidney has been examined using autoradiography. Saturation studies showed [3H]forskolin binding to two sites, a high affinity site (KD = 8.7 nM, Bmax = 0.14 pmol/mg protein) and a low affinity site (KD = 6.7 microM, Bmax = 11.0 pmol/mg protein). Autoradiographs showed high affinity binding (thought to identify stimulatory guanine nucleotide binding protein (Gs)-linked adenylate cyclase) to all renal structures known to possess hormone sensitive adenylate cyclase, including all tubular segments, glomeruli and blood vessels. High concentrations of binding were associated with a portion of the proximal tubule and with papillary collecting tubules and ducts.

Adenylyl Cyclases↗
PubMed1990

Differential regulation of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system after chronic (-)-isoproterenol infusion.

Quantitative autoradiography was used to determine the effects of chronic administration of (-)-isoproterenol (400 micrograms/kg/hr, 7 days) on the distribution and density of beta-1 and beta-2 adrenoceptors in guinea pig atrioventricular conducting system and surrounding regions. X-ray film was exposed to sections of heart labeled with (-)-[125I]-cyanopindolol in the absence or presence of ICI 118,551 (70 nM) to block beta-2 adrenoceptors, CGP 20712A (100 nM) to block beta-1 adrenoceptors or (-)-propranolol (1 microM) to define nonspecific binding. Quantitative autoradiography was performed using computer-assisted image processing and the AVID system. The proportions of beta-1 and beta-2 adrenoceptors were determined by the extent of inhibition of (-)-[125I]cyanopindolol binding by CGP 20712A (100 nM) together with equations which take into account the differing affinities of ligands for beta-1 and beta-2 adrenoceptors. In vehicle (1 mM HCl)-treated animals there was a higher density and proportion of beta-2 adrenoceptors in the atrioventricular node, bundle of His and right and left bundle branches than in myocardium. Chronic administration of (-)-isoproterenol produced marked loss of beta-2 adrenoceptor binding in all regions of the atrioventricular conducting system, surrounding myocardium, cardiac valves and the smooth muscle of the aorta accompanied by less pronounced effects on beta-1 adrenoceptors. Beta-1 adrenoceptors were significantly reduced only in the left bundle branch whereas there were trends toward a reduction in the right bundle branch, bundle of His and an increase in the atrioventricular node. There was no alteration in beta-1 adrenoceptor density in myocardium. Loss of beta adrenoceptor binding produced by (-)-isoproterenol was mainly confined to beta-2 adrenoceptors.

Animals↗
PubMed1989

New tools for the localization of second messenger systems.

1. Probes available for the localization of components of second messenger systems include G-protein oligonucleotides which have been used to produce cDNA probes to label G-protein mRNA by in situ hybridization histochemistry. 2. Enzymes involved in second messenger responses have been labelled with [3H]-forskolin (Gs-linked adenylate cyclase), [3H]-cAMP (cAMP-dependent protein kinase) and [3H]-PDBu2 (protein kinase C). 3. [3H]-Inositol 1,4,5 trisphosphate labels a site on sarcoplasmic reticulum believed to trigger Ca2+ release. 4. These probes allow the comparison of location of receptors and second messengers and the examination of changes in second messenger systems with drug treatment and disease.

Animals↗
PubMed1988

Autoradiographic localization and densitometric analysis of beta-1 and beta-2 adrenoceptors in the canine left anterior descending coronary artery.

The location and proportions of beta-1 and beta-2 adrenoceptors in canine coronary arteries (0.5-2 mm) has been examined by autoradiography. X-ray film and nuclear emulsion-coated coverslips were exposed to sections of coronary artery previously incubated with [125I]iodocyanopindolol (50 pM) in the absence and presence of ICI 118,551 (70 nM) to block beta-2 adrenoceptors, CGP 20712A (100 nM) to block beta-1 adrenoceptors or (-)-propranolol (1 microM) to define nonspecific binding. The medial smooth muscle of the coronary artery had an even distribution of beta-1 adrenoceptors and two populations of beta-2 adrenoceptors, one evenly distributed and the other highly localized. Beta-2 adrenoceptors were also located on nerve tissue and in the adventitia. There was no evidence for localization of beta adrenoceptors on endothelial cells. Quantitative autoradiography was performed using computer-assisted image processing and the program AVID. The binding of [125I]cyanopindolol was saturable (KD = 50 pM) and competition binding curves with the beta-1 selective antagonist CGP 20712A and beta-2 selective antagonist ICI 118,551 showed beta-1 and beta-2 adrenoceptors in the proportions of 85:15% in both 0.5- and 2-mm arteries.

Animals↗