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J X Wilson

Publications and source records attributed to J X Wilson.

63 records · Page 4Linked to original sources
PubMed1984

Inhibitory actions of calmodulin antagonists on steroidogenesis in zona glomerulosa cells.

The stimulation of aldosterone (Aldo) production in the adrenal glomerulosa cell by angiotensin II (AII) and ACTH is highly dependent on calcium. To determine the role of calmodulin (CM) as a regulator of intracellular calcium during hormonal activation of steroidogenesis, the actions of a series of CM inhibitors on the stimulation of Aldo biosynthesis by AII, the calcium ionophore A23187, ACTH, and cAMP were examined in isolated adrenal glomerulosa cells. The CM antagonists, pimozide, W7 [N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide] and W5 [N-(6-aminohexyl)-1-napthalenesulfonamide] caused dose-dependent inhibition of hormone-stimulated Aldo production, in proportion to their reported binding affinities for CM. The maximum inhibitory concentration (5 microM) of the most potent CM antagonist, pimozide, had no effect on the conversion of progesterone to Aldo. However, submaximal inhibitory concentrations of W7 and W5 also reduced conversion of progesterone to Aldo, indicating that their inhibitory action is not only due to their CM antagonist properties. The relative sensitivities of the stimuli of Aldo release to inhibition by all three CM inhibitors were A23187 = AII greater than ACTH greater than 8-bromo-cAMP (8-Br-cAMP). Aldo responses to ACTH were more sensitive to inhibition by pimozide than those to 8-Br-cAMP, suggesting that ACTH-induced cAMP formation is also dependent on CM. Pimozide (5 microM) completely inhibited the Aldo responses to AII and A23187, whereas the Aldo responses to ACTH and 8-Br-cAMP were only partially inhibited. At submaximal inhibitory concentrations, pimozide caused a decrease in the maximum response to AII without changing the concentration of the peptide required for half-maximum stimulation of Aldo production. The inhibition of Aldo production by pimozide was accompanied by parallel inhibition of pregnenolone accumulation measured in the presence of cyanoketone. No effect of pimozide (5 microM) was observed on the binding of 125I-AII to adrenal glomerulosa cells, placing the CM-dependent site between the receptor and the side-chain cleavage enzyme. These findings indicate that CM-mediated regulation is essential for the steroidogenic response to calcium ionophore and AII, but is only partially required for the responses to ACTH and 8-Br-cAMP.

Adrenal Cortex↗
PubMed1983

Mechanisms of action of corticotropin-releasing factor and other regulators of corticotropin release in rat pituitary cells.

The role of cyclic AMP in the stimulation of corticotropin (ACTH) release by corticotropin-releasing factor (CRF), angiotensin II (AII), vasopressin (VP), and norepinephrine (NE) was examined in cultured rat anterior pituitary cells. Synthetic CRF rapidly stimulated cyclic AMP production, from 4- to 6-fold in 3 min to a maximum of 10- to 15-fold at 30 min. Stimulation of ACTH release by increasing concentrations of CRF was accompanied by a parallel increase in cyclic AMP formation, with ED50 values of 0.5 and 1.3 nM CRF for ACTH and cyclic AMP, respectively. A good correlation between cyclic AMP formation and ACTH release was also found when pituitary cells were incubated with the synthetic CRF(15-41) fragment, which displayed full agonist activity on both cyclic AMP and ACTH release with about 0.1% of the potency of the intact peptide. In contrast, the CRF(21-41) and CRF(36-41) fragments were completely inactive. The other regulators were less effective stimuli of ACTH release and caused either no change in cyclic AMP (AII and VP) or a 50% decrease in cyclic AMP (NE). Addition of the phosphodiesterase inhibitor, methylisobutylxanthine, increased the sensitivity of the ACTH response to CRF but did not change the responses to AII, VP, and NE. In pituitary membranes, adenylate cyclase activity was stimulated by CRF in a dose-dependent manner with ED50 of 0.28 nM, indicating that the CRF-induced elevation of cyclic AMP production in intact pituitary cells is due to increased cyclic AMP biosynthesis. The intermediate role of cyclic AMP in the stimulation of ACTH release by CRF was further indicated by the dose-related increase in cyclic AMP-dependent protein kinase activity in pituitary cells stimulated by CRF with ED50 of 1.1 nM. These data demonstrate that the action of CRF on ACTH release is mediated by the adenylate cyclase-protein kinase pathway and that the sequence requirement for bioactivity includes the COOH-terminal 27 amino acid residues of the molecule. The other recognized regulators of ACTH release are less effective stimuli than CRF and do not exert their actions on the corticotroph through cyclic AMP-dependent mechanisms.

Adrenocorticotropic Hormone↗
PubMed1983

Catecholamine-mediated pressor responses to angiotensin II in the Pekin duck, Anas platyrhynchos.

Asp1,Val5-angiotensin II (AII) caused dose-dependent increases in aortic blood pressure (BP) when injected into anesthetized Pekin ducks. Norepinephrine (NE) and epinephrine (E) concentrations in arterial plasma were found to be elevated 1 min after injection of AII, when BP was peaking, while plasma levels of unconjugated dopamine (DA) did not undergo any consistent change. Pretreatment with 6-hydroxydopamine (6-OHDA) rendered ducks supersensitive to the pressor effect of injections of NE, but did not affect adrenal chromaffin cell granulation, plasma NE and E concentrations, or pressor responses to tyramine and AII. Depletion of endogenous NE and E stores, following treatment with reserpine, did not affect pressor responses to NE, but diminished pressor responses to tyramine and AII. The discrepancies in the responses of 6-OHDA-treated ducks and reserpinized ducks to exogenous NE and AII indicate different pressor mechanisms for the two hormones. It is suggested that mobilization of endogenous NE and E contributes to the rise in BP observed following AII injection.

Angiotensin II↗
PubMed1983

Neural mechanisms affecting pressor responses to angiotensins in the Pekin duck, Anas platyrhynchos.

1. Administration of SQ20881 diminished pressor responses to intravenous (i.v.) injections of angiotensin I (AI), but not those to injections of angiotensin II (AII), in Pekin ducks, indicating the occurrence of a mechanism similar to the mammalian angiotensin-converting enzyme reaction. 2. Pressor responses to AII were enhanced by general anaesthesia with phenobarbital, pentobarbital, or a combination of both phenobarbital and pentobarbital. 3. Ganglionic blockade with mecamylamine enhanced the pressor responses to AII and NE, but not those to tyramine, in anaesthetized ducks. 4. It is proposed that the potentiating effects of general anaesthesia and ganglionic blockade on pressor responses were due both to a lowering of baseline blood pressure (BP) and an inhibition of the neural reflexes which normally buffer BP. Furthermore, it is suggested that the augmented responsiveness of anaesthetized, ganglion-blocked ducks shows that the pressor effect of AII is predominantly of peripheral, rather than central nervous system (CNS), origin.

Angiotensin I↗
PubMed1983

Adrenalectomy inhibits noradrenergic, adrenergic, and vasopressor responses to angiotensin II in the Pekin duck (Anas platyrhynchos).

The iv injection of Asp1, Val5-angiotensin II(AII) was followed by increases in arterial plasma norepinephrine (NE) and epinephrine (E) concentrations and elevation of arterial blood pressure in the anesthetized Pekin duck. AII injection did not affect the concentration of unconjugated dopamine in arterial plasma. Adrenalectomy inhibited the increases in plasma NE and E concentrations elicited by AII. Pressor responses to AII also were diminished after adrenalectomy, whereas pressor responses to exogenous NE and tyramine were not measurably affected. The alpha-adrenergic blocking drug phenoxybenzamine diminished the pressor effect of AII in both shamoperated and adrenalectomized ducks. The blockade of alpha-adrenergic receptors by phenoxybenzamine was incomplete, since pressor responses to exogenous NE were lessened by not abolished. We conclude from these experiments that AII increases arterial blood pressure in the Pekin duck by mobilizing NE and E from both adrenal and extraadrenal stores. It remains unknown whether the residual pressor response to AII in phenoxybenzamine-treated, adrenalectomized ducks involves an alpha-adrenergic mechanism.

Adrenalectomy↗
PubMed1983

6-Hydroxydopamine treatment diminishes noradrenergic and pressor responses to angiotensin II in adrenalectomized ducks.

The extent to which the vasopressor action of angiotensin II (AII) in birds depends upon the sympathetic nervous system in not known. Therefore, we have tested whether the sympathetic neurotransmitter norepinephrine (NE) mediates the residual vasopressor response to AII in adrenalectomized ducks (Anas platyrhynchos). Treatment with 6-hydroxydopamine (6-OHDA) inhibited by up to 100% the pressor effect of exogenous AII in anesthetized adrenalectomized ducks. After high doses of AII, a transient drop in blood pressure (BP) often preceded or supplanted the pressor response. Systolic BP responses to injections of tyramine also were decreased by 6-OHDA, but responses to NE were increased (diastolic BP) or not affected significantly (systolic BP). Inhibition with SQ20881 of converting enzyme, to decrease endogenous production of AII, reduced pressor responses to AI, but did not affect either baseline BP or responses to AII. Thus, the diminished responsiveness to AII in these catecholamine-depleted ducks was not due to competition from endogeneous AII. Furthermore, the increases in plasma NE and E concentrations that normally follow AII injection were abolished by adrenalectomy and 6-OHDA treatment. The coincident extinction of both cathecholamine and vasopressor responses comprises new evidence that AII raises BP in the Pekin duck by stimulating the sympathetic nervous system. The vasopressor response is mediated by extraadrenal as well as adrenal sources of NE.

Adrenalectomy↗
PubMedDate not supplied

Ascorbate transport in pig coronary artery smooth muscle: Na(+) removal and oxidative stress increase loss of accumulated cellular ascorbate.

Pig deendothelialized coronary artery rings and smooth muscle cells cultured from them accumulated ascorbate from medium containing Na(+). The accumulated material was determined to be ascorbate using high-performance liquid chromatography. We further characterized ascorbate uptake in the cultured cells. The data fitted best with a Hill coefficient of 1 for ascorbate (K(asc) = 22 +/- 2 microM) and 2 for Na(+) (K(Na) = 84 +/- 10 mM). The anion transport inhibitors sulfinpyrazone and 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS) inhibited the uptake. Transferring cultured cells loaded with (14)C-ascorbate into an ascorbate-free solution resulted in a biphasic loss of radioactivity - an initial sulfinpyrazone-insensitive faster phase and a late sulfinpyrazone-sensitive slower phase. Transferring loaded cells into a Na(+)-free medium increased the loss in the initial phase in a sulfinpyrazone-sensitive manner, suggesting that the ascorbate transporter is bidirectional. Including peroxide or superoxide in the solution increased the loss of radioactivity. Thus, ascorbate accumulated in coronary artery smooth muscle cells by a Na(+)-dependent transporter was lost in an ascorbate-free solution, and the loss was increased by removing Na(+) from the medium or by oxidative stress.

Actins↗
PubMedDate not supplied

Antioxidant defense of the brain: a role for astrocytes.

Partially reduced forms of oxygen are produced in the brain during cellular respiration and, at accelerated rates, during brain insults. The most reactive forms, such as the hydroxyl radical, are capable of oxidizing proteins, lipids, and nucleic acids. Oxidative injury has been implicated in degenerative diseases, epilepsy, trauma, and stroke. It is a threshold phenomenon that occurs after antioxidant mechanisms are overwhelmed. Oxidative stress is a disparity between the rates of free radical production and elimination. This imbalance is initiated by numerous factors: acidosis; transition metals; amyloid beta-peptide; the neurotransmitters dopamine, glutamate, and nitric oxide; and uncouplers of mitochondrial electron transport. Antioxidant defenses include the enzymes superoxide dismutase, glutathione peroxidase, and catalase, as well as the low molecular weight reductants alpha-tocopherol (vitamin E), glutathione, and ascorbate (reduced vitamin C). Astrocytes maintain high intracellular concentrations of certain antioxidants, making these cells resistant to oxidative stress relative to oligodendrocytes and neurons. Following reactive gliosis, the neuroprotective role of astrocytes may be accentuated because of increases in a number of activities: expression of antioxidant enzymes; transport and metabolism of glucose that yields reducing equivalents for antioxidant regeneration and lactate for neuronal metabolism; synthesis of glutathione; and recycling of vitamin C. In the latter process, astrocytes take up oxidized vitamin C (dehydroascorbic acid, DHAA) through plasma membrane transporters, reduce it to ascorbate, and then release ascorbate to the extracellular fluid, where it may contribute to antioxidant defense of neurons.

Animals↗