Topography of 3H-DHA, 3H-QNB, 3H-dopamine, and 3H-DAGO binding sites distribution in the central part of the sinoatrial node in rat heart.

The topography of distribution of 3H-dihydroalprenolol, 3H-quinucledinyl benzilate, 3H-dopamine, and 3H-DAGO binding sites in the central part of the sinoatrial node in rat heart was studied by autoradiography after electrophysiological identification of the dominant pacemaker region location. Receptor asymmetry between the lateral and median regions of the central part of the sinoatrial node was shown. The dominant pacemaker region lay in the lateral area of the sinoatrial node; the number of binding sites for all four ligands was minimum in it. The number of binding sites gradually increased in the cranial and caudal directions from the dominant pacemaker region along the sinoatrial node artery (more smoothly in the caudal direction). The relative densities of bindings sites for 3H-dihydroalprenolol and 3H-dopamine were higher in the lateral region compared to the perinodal working myocardium, while the densities for 3H-quinucledinyl benzilate and 3H-DAGO were virtually the same. The distribution of binding sites along the artery in the median region of the sinoatrial node was even for 3H-quinucledinyl benzilate and 3H-DAGO. For 3H-DAGO these parameters were close to those in the perinodal atrial myocardium, for 3H-quinucledinyl benzilate somewhat lower. Curves presenting the distribution of binding site densities for 3H-dihydroalprenolol and 3H-dopamine in the median region of the sinoatrial node were similar, with a pronounced peak in the region contralateral to the dominant pacemaker region, and significantly higher binding parameters compared to those for the perinodal atrial myocardium. The difference consisted in higher density of 3H-dopamine binding sites in the median region of the sinoatrial node in comparison with the lateral region. Binding activity was maximum in the wall of the sinoatrial node artery. The distribution of binding sites for ligands to the main autonomic nervous system neurotransmitters in the rat heart sinoatrial node is heterogeneous.

Post-transcriptional induction of beta 1-adrenergic receptor by retinoic acid, but not triiodothyronine, in C6 glioma cells expressing thyroid hormone receptors.

Thyroid hormone (triiodothyronine; T3) has been shown to control the expression of beta 1-adrenergic receptors (beta 1-AR) in cardiac myocytes, but not in C6 glioma cells. This cell specificity has been attributed to low expression of T3 receptors and high expression of the c-erbA alpha 2 splice variant that interferes with the action of T3. To check this hypothesis we have expressed the c-erbA/thyroid hormone receptor (TR) alpha 1 gene in C6 glioma cells and investigated their response to thyroid hormone. Cells expressing TR alpha 1, but not wild-type cells, were responsive to T3 as shown by increased expression of mitochrondrial hydroxymethylglutaryl CoA synthase after T3 exposure. However, T3 had no effect on beta 1-AR gene expression in either set of cells. The beta 1-AR mRNA concentrations were, however, altered by retinoic acid (RA) treatment. Retinoic acid caused a rapid up-regulation of beta 1-AR mRNA levels that was blocked by cycloheximide. Retinoic acid did not increase the beta 1-AR gene transcription rate in run-on experiments. These results indicate an indirect post-transcriptional effect of RA. Control of beta 1-AR expression in C6 cells is also exerted at the translational level, because there was no correlation between mRNA and protein induction, as determined by radioligand binding studies. We conclude that lack of responsiveness of the beta 1-AR gene in C6 cells to T3 is not due to high expression of c-erbA alpha 2 but to undefined cell-specific factors.

Cardiac beta receptors' density or affinity modified by different Trypanosoma cruzi amount.

Chagas' disease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and antagonist studied at 30 days post-infection (p.i). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with 3H/DHA. The AcH group presented less cardiac beta receptors number (p < 0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p < 0.01) but density was not different from non infected animals. beta receptors' affinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy.

Cardiac beta receptors' density or affinity modified by different Trypanosoma cruzi amount

Chagas'disease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and anatogonist studied at 30 days post-infection (p.i.). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with (3)H/DHA. The AcH group presented less cardiac beta receptors number (p<0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p<0.01) but desinty, was not different from non infected animals. Beta receptors'affinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy.

Cardiac beta receptors density or affinity modified by different Trypanosoma cruzi amount

Chagasdisease presents complex physiopathogenic mechanism, many of them poorly understood, that in our country generally produce cardiac lesions. The acute phase related with the presence of the parasite is usually asymptomatic. This report studies if the amount of T. cruzi that induced acute infection could modify the myocardiopathy evolution. Previous works have shown that Albino Swiss mice inoculated with 45 tripomastigotes (AcL) presented alterations in the cardiac pharmacological response to adrenergic agonist and anatogonist studied at 30 days post-infection (p.i.). Mice inoculated with 7 x 10(4) parasites/animal showed similar behaviour at 7 days p.i. We studied the involvement of the affinity and density of cardiac beta receptors in both acute groups by binding with (3)H/DHA. The AcH group presented less cardiac beta receptors number (p<0.001), but their affinity was conserved. The AcL model presented significantly less affinity (p<0.01) but desinty, was not different from non infected animals. Beta receptorsaffinity of both infected groups were similar, but AcH density was significantly diminished when compared with AcL. These studies demonstrates that the amount of T. cruzi received by the host determines and acelerates the evolution of the chagasic myocardiopathy. (AU)

[Age-dependent changes in the adenylate cyclase system of rat ventral prostate].

Changes in beta-adrenoceptors, GTP binding (G) proteins and adenylate cyclase (AC) activity of ventral prostates of rats during aging were studied in these experiments. The density of beta-adrenoceptors increased markedly after birth, reaching a maximum in the tissues at 16 weeks of age and remained at this level for about 90 weeks. When stimulated by isoproterenol, the AC activity increased 4- and 22-fold in 2- and 8-week-old rats, respectively, but only 7-fold in both 16- and 104-week-old rats. Activation of AC by forskolin was the greatest during the 2 weeks after birth and then showed a sharp decrease, reaching a plateau in the tissues at 8 weeks. Bmax value of [35S]GTP gamma S binding to the tissues was the largest at 8 weeks. Pretreatment of the tissues with pertussis or cholera toxin caused age-dependent changes in both the binding abilities of Gi and Gs proteins to GTP that coincided with changes in the binding of G proteins to GTP. There was no difference between the abilities of Gi and Gs proteins to bind to GTP in the tissues of rats of the respective age. These results show that changes in the binding ability of G proteins to GTP influence the function of ventral prostates of rats during the aging process, and this is mediated through the regulation of AC activity.

Increased beta-adrenergic receptor density in an experimental model of cardiac transplantation.

We examined beta-adrenergic receptor density, basal, maximal isoproterenol and fluoride-stimulated adenylate cyclase activities, and morphologic characteristics of rabbit and rat native and heterotopic isograft cardiac tissue. Four weeks after graft placement there were only subtle histologic differences between native and graft tissue. Membrane preparations from isografts of rabbits demonstrated increases in beta-receptor density (maximum [3H]DHA binding = 111 +/- 19.3 fmol/mg versus 52.4 +/- 4.9 in native hearts, p less than 0.05). In a small number of experiments, rat isografts also demonstrated a suggestive increase in beta-receptor density (69.8 +/- 7.1 fmol/mg versus 40.2 +/- 7.3 in native hearts). Isoproterenol-stimulated adenylate cyclase activity was greater in rabbit graft hearts (3.98 +/- 0.20 X basal activity) than in native tissue 2.67 +/- 0.16 X basal activity, p less than 0.05). We conclude that cardiac denervation may lead to a postsynaptic form of beta-adrenergic supersensitivity that is due to an increase in beta-receptor density.