Showing papers by "Michel Bouvier published in 1987"

Cross-talk between cellular signalling pathways suggested by phorbol-ester-induced adenylate cyclase phosphorylation.

Abstract: Receptor-mediated activation of both adenylate cyclase and phosphatidylinositide hydrolysis systems occurs through guanine nucleotide regulatory proteins and ultimately leads to specific activation of either cyclic AMP-dependent protein kinase A or Ca2+/phospholipid-dependent protein kinase C. Given the remarkable diversity of agents that influence cellular metabolism through these pathways and the similarities of their components, interactions between the two signalling systems could occur. In fact, stimulation of cells with 12-O-tetradecanoyl phorbol-13-acetate (TPA), a phorbol ester that activates protein kinase C, influences hormone-sensitive adenylate cyclase. In some cells TPA induces desensitization of receptor-mediated stimulation of adenylate cyclase, whereas in others, such as frog erythrocytes, phorbol ester treatment results in increased agonist-stimulated as well as basal, guanine nucleotide- and fluoride ion-stimulated adenylate cyclase activities. We show here that TPA produces phosphorylation of the catalytic unit of adenylate cyclase in frog erythrocytes. Moreover, purified protein kinase C can directly phosphorylate in vitro the catalytic unit of adenylate cyclase purified from bovine brain. These results suggest that phosphorylation of the catalytic unit of adenylate cyclase by protein kinase C may be involved in the phorbol ester-induced enhancement of adenylate cyclase activity. In addition to providing the first direct demonstration of a covalent modification of the catalytic unit of adenylate cyclase, these results provide a potential biochemical mechanism for a regulatory link between the two major transmembrane signalling systems.

Abnormal regulation of the sympathoadrenal system in deoxycorticosterone acetate-salt hypertensive rats.

Abstract: With the use of circulating norepinephrine (NE) and epinephrine (E) levels, the sympathoadrenal activity as well as its local modulation by adrenoceptors were studied in normotensive (NT) and DOCA-salt hypertensive (HT) rats. In anesthetized hypertensive rats, plasma NE levels were higher, whereas in conscious animals both NE and E levels were found to be increased, suggesting an increased basal sympathoadrenal tone in these animals. The finding of a close correlation between blood pressure levels and NE levels suggests that the elevation of blood pressure may be linked to sympathetic system activity in this experimental model of hypertension. The reactivity of the sympathoadrenal system was also found to be increased in DOCA HT rats. Following a bilateral carotid occlusion of 1 min, which specifically activates the adrenal medulla, the elevation of E levels was found to be potentiated in intact or vagotomized HT rats. Moreover, in response to prolonged or acute hypotension in anesthetized and conscious animals, the elevation in plasma NE and E levels was found to be markedly potentiated in DOCA HT rats. The local modulating adrenoceptor-mediated mechanisms of the sympathoadrenal system appeared to be altered in this model of hypertension. Although it was possible to demonstrate that the E response to carotid occlusion can be greatly potentiated by administration of an alpha2-antagonist (yohimbine) and completely abolished by an alpha2-agonist (clonidine) in NT rats, the E response was found to be unaffected by the same treatments in HT rats, suggesting a reduced sensitivity in the alpha2-mediated inhibitory modulation of the adrenal medulla. Moreover, the acute treatment with a beta-blocker (sotalol) lowered circulating NE levels and blood pressure only in HT rats, suggesting the possibility of a more sensitive beta-receptor-mediated presynaptic facilitatory mechanism on sympathetic fibers of these animals. Finally, it was observed that the functional balance which exists between the activities of sympathetic fibers and the adrenal medulla in normotensive animals appears to be impaired in DOCA HT rats. In conclusion, the present studies suggest that the increased sympathoadrenal tone and reactivity may be due, in part, to a variety of dysfunctions in local adrenoceptor modulatory mechanisms of the sympathoadrenal system in DOCA hypertensive rats.

Effects of morphine on electrical activity of the rectum in man.

Abstract: 1. The effects of morphine on the electrical activity of the human rectum were investigated. 2. In healthy volunteers, morphine (0.04-0.16 mg/kg, i.v.) induced spike activity that could become cyclical. 3. All the effects of morphine were antagonized by naloxone (0.03-0.2 mg/kg, i.v.), but not blocked by atropine (0.007-0.014 mg/kg, i.v.). 4. In patients with spinal cord injury, morphine was observed to have similar excitatory effects. Spinal cord transection was complete in all patients, so that participation of supraspinal nervous structures in these effects could be ruled out. The sacral parasympathetic nervous centres could not have been involved in two patients in whom the medullary cone was also destroyed. The thoracolumbar sympathetic nervous centres were not completely destroyed in any of the patients, however, so that the possibility that these centres may have been involved cannot be entirely ruled out. 5. Morphine failed to activate an aganglionic rectum in a patient with Hirschsprung's disease, indicating that it had no direct effect on smooth muscle cells. It is therefore probable that morphine may have an effect on the intrinsic innervation.

Red blood cell catecholamine levels in normotensive and DOCA-salt hypertensive rats

Abstract: Under basal conditions in anesthetized rats, significant concentrations of free norepinephrine (NE), epinephrine (E), and dopamine (DA) were detected in red blood cell (RBC) lysate. These concentrations were not proportional to their respective plasma concentrations and thus RBC-to-plasma concentration ratios were different for each catecholamine (CA). DA was by far the most concentrated amine inside the RBC. An acute increase in plasma NE and E levels, induced by hemorrhagic hypotension in normotensive (NT) rats, did not result in any modification of the RBC CA content. However, chronic elevation of the NE plasma levels in bilaterally adrenalectomized rats and in deoxycorticosterone acetate (DOCA)-salt hypertensive rats (DOCA-salt HT) were associated with increased NE levels in the RBC. In addition, the large elevation in plasma E concentrations following hemorrhagic hypotension in DOCA-salt HT rats, as well as the greater plasma NE response to hypotension in adrenalectomized animals, were accompanied by increases in the respective RBC amine concentrations. During a steady-state intravenous infusion of tritiated NE, we observed a slow accumulation of radioactivity inside the RBC, indicating that CA can enter the RBC from the plasma. Moreover, catechol methyltransferase activity was measured in the cytosolic fraction of the RBC of both NT and DOCA-salt HT rats suggesting that, once inside the RBC, the catecholamines can be metabolized.