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Biomedical subjects

A R Morrison

Publications and source records attributed to A R Morrison.

At least 145 records · Page 8Linked to original sources
PubMed1982

Effects of angiotensin II on phosphatidylinositol and polyphosphoinositide turnover in rat kidney. Mechanism of prostaglandin release.

Prostaglandin (PG) release from rat inner medullary tissue has been shown to be stimulated by angiotensin II, bradykinin, and arginine vasopressin. PG release from inner medullary has also been demonstrated to be a Ca2+-dependent process. We performed the following studies in an attempt to determine the mechanism by which angiotensin II stimulates PG release and to identify the lipid source serving as the donor for arachidonic acid (AA) in the Ca2+-dependent reaction. After 5 min of incubation, slices of inner medulla prelabeled with [14C]AA released 2.0-fold as much radiolabel into the media in the presence of Ca2+ as in the absence of Ca2+. After 30 min of incubation, the neutral lipids lost 6.1% of their [14C]AA label, phosphatidylethanolamine lost 12.5%, phosphatidylcholine 13.3%, and phosphatidylinotisol (P[I) 27%. The divalent ionophore A23187 (5 microM) increased 3.7-fold the formation of immunoassayable prostaglandin E2 at 30 min in the presence of Ca2+. Angiotensin II increased immunoassayable PGE2 formation 1.3-fold at 2 min and 1.5- to 1.8-fold by 30 min. In addition, angiotensin II rapidly increased the incorporation of [32P]orthophosphate to significantly higher values into PI, phosphatidic acid, diphosphoinositol, and triphosphoinositol by 30 s, returning to control values by 2 min of incubation. The data suggest that PI may be a major source of arachidonic acid in the Ca2+-dependent release of PG, that angiotensin II stimulates a smaller or different pool of AA release than the divalent ionophore, and the angiotensin II stimulation of PG is a Ca2+-mediated process associated with increased "phosphatidylinositol-polyphosphoinositide" turnover in the rat inner medulla.

Angiotensin II↗
PubMed1982

Different behaviors during paradoxical sleep without atonia depend on pontine lesion site.

Bilateral pontine tegmental lesions in cats release a state of paradoxical sleep (PS) without atonia that possess all other electrographic criteria of PS. PS without atonia has been previously considered as a unitary phenomenon, but the present work demonstrates that different behavioral syndromes result from different lesion placements. Five of 25 cats exhibited the minimal syndrome of increased proximal limb and head movements. The head was not raised; and coordinated behavior was not seen. The nuchal electromyogram (EMG) showed tone for 25-100% of such an episode. Selective destruction of the origin (n = 2) or caudally projecting fibers (n = 1), of the tegmentoreticular pathway released this minimal syndrome of unorganized limb and head movements. This pathway had previously been proposed to mediate atonia, but the present work demonstrates that additional damage is necessary to release tone completely as well as the elaborate behaviors discussed below. Eight cats raised their heads, righted their forequarters, and moved head, neck and forelimbs in movements resembling orienting, staring, reaching and attempting to stand. The lesions releasing such behavior were centered at P = 3.0, H = 2.0, V = -4.0, and damaged a region projecting to the superior colliculus. Two cats with slightly more ventral lesions did not exhibit the orienting behavior. Six cats demonstrated violent phasic behavior resembling attack punctuating tonic periods of quiet staring or searching movements. Attack resulted from damage extending rostroventrally into the midbrain at P = 2.0, H = 2.5, V = -4.5 (4/6) or from unilateral damage to a lateral pathway arising in the central amygdalar nucleus (2/6). In 4 cats, coordinated fore- and hindlimb activation resulted in locomotion during PS. Walking resulted from larger, more ventral lesions centered at P = 3.0, H = 2.0, V = -5.5. Considering the anatomy of the lesions in relationship to brain stem systems known to play a role in orienting, attack and locomotion, we conclude that inhibitory systems were damaged by these lesions and that PS without atonia is not simply a state during which neural activity of normal PS can be expressed behaviorally.

Amygdala↗
PubMed1981

Raphe unit activity during REM sleep in normal cats and in pontine lesioned cats displaying REM sleep without atonia.

Previous studies have shown that the activity of serotonin-containing raphe neurons in cats is almost completely suppressed during rapid eye movement (REM) sleep. However, since raphe unit activity is known to be grossly correlated with the level of behavioral arousal or tonic motor activity, this decrease in activity during REM sleep may be simply due to the fact that tonic EMG activity or motoric output is at a minimum. On the other hand, raphe unit activity may be related to the state (i.e. REM sleep) of the organism. To test these competing hypotheses, in the present study we compared raphe unit activity in normal cats with that in cats that display REM sleep without atonia (produced by bilateral lesions of the pontine tegmentum). These lesioned cats manifest episodes which, by all criteria, appear to be REM sleep except that they display overt behavior, presumably because the mechanism normally responsible for producing atonia has been disrupted. Although the activity of raphe neurons in lesioned cats during REM sleep without atonia was significantly below that seen in these cats during waking, the level of activity was often impressive. This is especially true when those animals that displayed the greatest degree of tonic motor activity during REM sleep (group IV animals) are considered separately. In these cats, the depression was only 40.5% below their quiet waking level, whereas in lesioned cats displaying less tonic motor activity (Group II animals), raphe discharge rate was 65.6% below their quiet waking level. The discharge rate of raphe neurons during REM sleep in lesioned cats was more than 6-fold greater than that seen in normal animals. These data, in conjunction with other recent results from our laboratory, suggest that the decrease in raphe unit activity during REM sleep is largely a concomitant of the atonia which characterizes that state. These data are discussed within the general context of the relationship between raphe unit discharge and the activity of central motor systems.

Animals↗
PubMed1981

Regional synthesis of monohydroxy eicosanoids by the kidney.

Arachidonic acid was incubated with 10,000 X g and 100,000 X g supernatants prepared from the medullae of hydronephrotic, normal, and contralateral rabbit kidneys. Metabolites whose production was calcium dependent but not inhibited by indomethacin were identified by thin layer chromatography. Preparative separation was carried out by silicic acid high pressure liquid chromatography. The methyl ester trimethylsilyl derivatives were prepared and examined by gas chromatography-mass spectrometry. The mass spectra matched previously published mass spectra for 12-hydroxy-5,8,10,14-eicosatetraenoic acid and 15-hydroxy-5,8,11,13-eicosatetraenoic acid. The renal cortex does not metabolize arachidonic acid through the lipoxygenase pathway. Thus, there is regional metabolism of arachidonate to monohydroxy eicosanoids in the kidney.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗
PubMed1981

Spontaneous and elicited PGO spikes in rats.

High-amplitude waves, similar in distribution and configuration to ponto-geniculo-occipital (PGO) spikes recorded in cats, were recorded from the area of the locus coeruleus of chronically implanted, unanesthetized albino rats. The mean frequency of spiking during paradoxical sleep (PS) was 19 per min and the amplitudes of the spikes ranged from 0.07 to 0.28 mV. Based on these findings and those of a previous report, it was concluded that these spikes are homologous with PGO spikes recorded in cats. It was also found that spikes identical to the spontaneously occurring spikes of PS could be produced during wakefulness and in all states of sleep with external auditory stimulation. These elicited spikes were not accompanied by eye movements. Initial stimulus presentations resulted in EEG desynchronization, orienting movements and PGO spikes. With continued stimulus presentations, EEG and other signs of alerting would habituate followed by a gradual habituation of the spikes. The latency to the appearance of an evoked spike ranged from 20 to 24 msec. These findings are in agreement with recent studies in cats showing that PGO spikes occur in response to external, auditory stimuli in wakefulness and all stages of sleep in addition to their spontaneous occurrence just prior to and during PS.

Animals↗
PubMed1981

A disorder of rapid eye movement sleep in a cat.

A young female cat with no neurologic abnormality during wakefulness was discovered to have violent motor activity during rapid eye movement sleep. Various characteristics of the disorder, which differentiated these episodes from epileptic seizures, suggested that the movements resulted from an exaggeration of phasic excitation during rapid eye movement sleep.

Animals↗
PubMed1981

Thromboxane A2 is the major arachidonic acid metabolite of human cortical hydronephrotic tissue.

Human cortical hydronephrotic microsomes converted [14C] arachidonic acid to [14C] thromboxane B2 as the major metabolic product. Using [14C] PGH2 as substrate, similar enzymatic conversions were noted with HHT greater than TXB2 less than 6KPGF1 alpha greater than PGE2 greater than PGE2 alpha as the major products. Inhibition of thromboxane synthetase with imidazole 5 mM reduced thromboxane B2 production by 60% and the major product then was 6 keto PGF1 alpha. After addition of imidazole, the metabolic profile showed PKPGF1 alpha greater than PGE2 greater than HHT greater than PGF 2 alpha. Control experiments were carried out using normal cortical tissue obtained from kidneys removed surgically for carcinoma of kidney and rejected for transplantation secondary to fracture as a consequence of blunt trauma. These control kidneys, while they demonstrated an ability to generate thromboxane B2 in vitro, had much less activity than hydronephrotic kidneys and with PGH2 as substrate PGE2 greater than TxB2. In addition, inhibition with imidazole produced mainly PGE2. Thus, like the rabbit and rat, there is enhanced thromboxane and prostacyclin synthesis in human ureteral obstruction and are, therefore, potential vasoactive compounds which may in part be responsible for the hemodynamic alterations occurring in human obstructive uropathy.

6-Ketoprostaglandin F1 alpha↗
PubMed1981

Metabolism of arachidonate through NADPH-dependent oxygenase of renal cortex.

In normal kidneys the renal medulla very efficiently converts arachidonic acid to prostaglandins. Although the renal cortex has only trace amounts of cyclooxygenase activity, we report here the existence of an active cortical NADPH-dependent monooxygenase that converts arachidonate primarily into 19-hydroxy- and 20-hydroxyarachidonate as well as 19-ketoarachidonate and a dicarboxylic acid. The enzyme is presumably a cytochrome P-450 monooxygenase and demonstrated marked resistance to inhibition by 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A), metyrapone, and carbon monoxide. In the rabbit kidney these products are produced only by the cortex in the presence of NADPH and represent the major metabolic products of arachidonate metabolism.

Animals↗
PubMed1981

The relationship of excessive exploratory behavior in wakefulness to paradoxical sleep without atonia.

The hypothesis that cats exhibiting paradoxical sleep (PS) without atonia are more active than normal in wakefulness was tested. To provide a quantitative measure of locomotor activity, 15 cats were subjected to an open-field test of activity for 5 one-hour or 10 half-hour sessions before and after placement of bilateral pontine tegmental lesions, which induce PS without atonia. Thirteen of the cats had PS without atonia and showed significant (p less than 0.05) increases in open-field activity, which was judged to be exploratory in nature, rather than aimless pacing. Increases ranged from 30-261%. In spite of the abnormal increase in antigravity muscle tone during PS postoperatively, hypertonia was not present during wakefulness. Of the 2 cats without elaborate behavior during PS, 1 had a significant decrease in activity. Its lesion may have damaged a lateral brainstem locomotor region. The same effect was obtained with unilateral damage of this region in 1 of 2 cats subjected to 2-stage operations. The results were used to develop the argument that peripheral motor inhibition during PS depends on suppression of a brainstem locomotor region in addition to direct inhibition of spinal motor neurons.

Animals↗
PubMed1980

Production of thromboxane A2 by the kidney in glycerol-induced acute renal failure in the rabbit.

The hemodynamic alterations occuring in glycerol induced renal failure are controversial. To date no single humoral substance can fully explain the change in renal resistance observed in this hemodynamic model of acute renal failure. To assess the capacity of the rabbit kidney to produce thromboxane A2, a potent vasoconstrictor, the following experiments were carried out. Rabbits received 14 ml/kg of 50% glycerol subcutaneously 24 hrs before the study. After 24 hrs., the kidneys were removed and perfused ex vivo in superfusion bioassay cascade. Kidneys from rabbits which developed renal failure, as assessed by elevated serum creatinines, released a substance which produced contraction of rabbit aorta (RCS) in response to bradykinin (BK) and angiotensin II. Microsomes prepared from these kidneys when incubated with [14C]-arachidonic acid produced a peak of radioactivity which comigrated with thromboxane B2 on the thin layer chromatography and was inhibited by the thromboxane synthetase inhibitor imidazole. Furthermore, an inverse linear relation was found between the BK dose required to release RCS from perfused kidney and the serum creatinine levels. A direct linear relation was found between the percent of TxB2 produced by renal microsome preparations and the serum creatinine. These studies demonstrate an increased renal capacity of the glycerol-model of acute renal failure to produce TxA2. The production of TxA2 a potent vasoconstrictor should therefore be further evaluated as a potential endogenous mediator of the hemodynamic changes occurring in acute renal failure.

Acute Kidney Injury↗