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Biomedical subjects

W W Morgan

Publications and source records attributed to W W Morgan.

At least 73 records · Page 4Linked to original sources

Use of liquid chromatography with electrochemistry to measure effects of varying intensities of white light on DOPA accumulation in rat retinas.

Exposure of dark-adapted rats to light enhances the activity of the retinal dopamine (DA) neurons. The purpose of this study was to determine if the response of these neurons to light varies with different intensities of light. The accumulation of dihydroxyphenylalanine (DOPA) after inhibition of L-aromatic amino acid decarboxylase with NSD-1015 was used as a measure of the in vivo activity of these DA neurons. Retinal DOPA accumulation was significantly increased in dark-adapted rats that had been exposed to light for only 5 min. The activation of the retinal DA neurons by cool white fluorescent lighting was dependent upon the light intensity. Light intensities of 0.1 and 0.5 lux did not stimulate the retinal DA neurons. There was a significant, but submaximal, activation of the neurons by 5.0 lux, and intensities of 32.2 lux or more maximally stimulated the neurons. The method involving liquid chromatography (LC) with electrochemistry (EC) which was used in these experiments to measure retinal DOPA and DA concentrations is also described in detail.

Animals↗

The use of gabaculine-induced accumulation of GABA for an index of synthesis of GABA in the retina.

The characteristics of accumulation of gamma-aminobutyric acid (GABA) in the retina after an intravitreal injection of the GABA-T inhibitor, gabaculine, have been studied in rats. The accumulation of GABA after injection of gabaculine was both dosage- and time-dependent. In both dark- and light-adapted-retinas. GABA continued to increase linearly for at least 90 min after an injection of gabaculine and this increase (3-fold) was similar in dark- and light-adapted rats. The GABA agonist, muscimol, and the GABA antagonist, bicuculline methiodide, significantly inhibited and facilitated, respectively, the gabaculine-induced increase in GABA levels. Previous studies have shown that accumulation of GABA following the irreversible inhibition of GABA-T was useful for measuring the rate of synthesis of GABA in the central nervous system, and these studies suggest that this technique may also be useful in the retina.

Adaptation, Ocular↗

Postnatal development of the light response of the dopaminergic neurons in the rat retina.

The effect of light on retinal dopamine (DA) synthesis and content in dark-adapted rats was assessed 15 h and 2, 4, 7 and 16 days after eye opening (13 to 14 days after birth). The accumulation of dihydroxyphenylalanine (DOPA) following inhibition of its decarboxylation was used to estimate DA synthesis. At 7 and 16 days, but not earlier, light significantly augmented DOPA formation. These increases were as dramatic as those reported for adult rats. DA in dark-adapted retinas ranged from 0 (undetectable) at 15 h to 83% of adult levels at 16 days, but were only 36% of that of adult retinas at 7 days. Light produced a significant decline in DA at 16 days but not at any other time point. These results indicate that the dopaminergic neurons synthesize transmitter and respond to light at a time when the neuronal pools of DA are not yet mature.

Aging↗

Reduced dopamine synthesis and protein levels in the median eminence of blinded anosmic female rats: relation to the pineal.

Twenty 25 day old female Sprague-Dawley rats were enucleated (BL) and olfactory bulbectomized (ANOS) and one half of these were also pinealectomized (PINX). Ten female rats received no surgical manipulation (CONTROL). Thirty days later each rat received NSD-1015 30 minutes before killing. The median eminence, telencephalon and hypothalamus were collected. Tyrosine hydroxylase activity, determined by the accumulation of DOPA after NSD-1015, was significantly reduced in the median eminence of BL+ANOS (p less than 0.05). Dopamine and noradrenaline levels in this tissue were not different among the experimental groups. Protein levels in the median eminence was also significantly reduced in BL+ANOS and PINX rats. None of the above parameters were different in the hypothalamus among the 3 experimental groups. These data suggest that the activity of the dopaminergic tuberoinfundibular neurons is reduced in both BL+ANOS and PINX rats. The reduced protein may reflect a reduction in protein synthesis, a decrease in numbers of nerve terminals or a reduction of pituitary regulatory hormones in BL+ANOS and PINX rats.

Animals↗

Pineal indoleamine metabolism in the cotton rat, Sigmodon hispidus: studies on norepinephrine, serotonin, N-acetyltransferase activity and melatonin.

The purpose of this study was to examine the levels of norepinephrine (NE), serotonin, melatonin and N-acetyltransferase (NAT) activity in the cotton rat pineal gland in relationship to environmental lighting. In each of two experiments cotton rats were collected from the wild and housed indoors in a 14:10 light:dark (LD) cycle (lights on at 0600) for a period of at least two weeks. Pineal glands were removed from animals in groups of eight at 0800, 1200, 1600, 2000, 2400, 0200 and 0400 hours over a 24 hour period for each experiment. Collection was done under a dim red light during the nighttime hours. In the first experiment pineal melatonin production showed a striking circadian rhythm with nighttime levels 20 times greater than that of daytime levels. In the second experiment pineal NE, serotonin and NAT activity were measured in aliquots from the same gland. NE showed no circadian rhythm whereas serotonin values were significantly depressed at night. The nighttime NAT activity rose to 10 times that of the daytime level. The NAT peak was concurrent with the melatonin peak. These data indicate that the neural and the biochemical control of the cotton rat pineal may be similar to that of other mammalian species.

Animals↗

GABA antagonists enhance dopamine turnover in the rat retina in vivo.

Previous results provided evidence for an inhibitory GABAergic influence on the dopamine neurons of the rat retina, without proving that endogenous GABA physiologically regulates the activity of these cells. We injected picrotoxinin intraocularly to dark-adapted rats and measured retinal dopamine turnover. Dopamine was analyzed radioenzymatically, and the decline in dopamine after alpha-methyl-p-tyrosine was used as an index of dopamine turnover. Picrotoxinin significantly stimulated dopamine turnover (P less than 0.05). In similar experiments with light-exposed rats picrotoxinin slightly enhanced dopamine turnover beyond that produced by light alone. Intraocular bicuculline methiodide produced similar results in dark-adapted and also in light-exposed rats. These data suggest that endogenous GABA tonically inhibits the activity of the retinal dopamine neurons in the dark and that there may be some remaining GABA tone on these cells in the light-exposed rat. Atropine pretreatment did not affect the picrotoxinin-induced activation of retinal dopamine turnover which negates the involvement of a cholinergic interneuron.

Adaptation, Physiological↗

Early response of the dopaminergic tuberoinfundibular neurons to anterior pituitary homografts.

Two anterior pituitary homografts were inserted under the left kidney capsule of adult male Sprague-Dawley rats (experimental rats). Sham-treated rats were exposed to identical surgical manipulations, but no tissue was inserted under the kidney capsule. The concentrations of dopamine (DA) and noradrenaline (NA) were determined in the median eminence, intermedioposterior pituitary and telencephalon by a radioisotope-enzyme technique. The decline in DA or NA 2 h after treatment with alpha-methyl-p-tyrosine provided a measure of DA and NA turnover, respectively. A marked increase in DA turnover was observed in the median eminence of the experimental compared to the sham-treated rats at 1, 3 and 6 days following surgery. The concentrations of DA and NA were significantly reduced in the median eminence of the experimental rats compared to sham-treated rats at both 3 and 6 days following surgery. No statistically significant increases in DA or NA turnover were observed in either the intermedioposterior lobe of the pituitary or the telencephalon of the experimental animals compared to the sham-treated animals at any time investigated. Serum prolactin (PRL) levels were significantly elevated in the experimental animals compared to the sham-treated animals by 3 days following surgery. The results of these studies clearly show that the turnover of DA in the terminals of the tuberoinfundibular neurons is increased by 1 day following the transplantation of anterior pituitary homografts under the kidney capsule. Future studies will be required to determine if this response is due exclusively to an early increase in serum PRL levels.

Animals↗

Comparative inotropic response of newborn and adult rabbit papillary muscles to isoproterenol and calcium.

Age-related changes in the response rabbit papillary muscles to isoproterenol and calcium were studied. Newborn rabbit papillary muscles were not only less sensitive to the inotropic effect of isoproterenol and calcium, but also produced significantly less maximal inotropic tension to these agents in comparison to the adult. The decreased response of newborn papillary to isoproterenol appears to be due to a combination of (a) decreased ability of papillary muscle to respond to calcium and (b) immaturity of isoproterenol-sensitive contractile mechanism. Differences in myocardial norepinephrine content do not appear to play an important role in the age-related difference in the response to isoproterenol and calcium.

Age Factors↗

Evidence for a cholinergic influence on catecholaminergic pathways terminating in the anterior and medial basal hypothalamus.

Adult male Sprague-Dawley rats were given hourly injections of physostigmine for 1--4 h, and the effect of this treatment on dopamine (DA) and noradrenaline (NA) content or on DA and NA was estimated by measuring the decline in these amines produced following the inhibition of tyrosine hydroxylase with alpha-methyl-p-tyrosine (alpha MPT). In later experiments oxotremorine was administered instead of physostigmine at hourly intervals for 2 h. Physostigmine administration resulted in a highly significant increase in the depletion of NA produced by alpha MPT indicating that the turnover of NA was increased by this drug. This effect was observed in the medial basal hypothalamus and anterior hypothalamus but not in the telencephalon-thalamus. Oxotremorine also produced an increase in NA turnover, but this drug was effective in all three brain areas. Atropine pretreatment blocked the effect of both physostigmine and oxotremorine on NA turnover. However, in the case of physostigmine, atropine was only effective if it was given 30 min before each injection of physostigmine. Mecamylamine, a nicotine blocker, did not reverse the effect of physostigmine on NA turnover. These results suggest that there is a cholinergic input via muscarinic receptors which influences the activity of noradrenergic pathways terminating in the anterior or medial basal hypothalamus.

Animals↗

Time course of the disappearance of pineal noradrenaline following superior cervical ganglionectomy.

Pineal glands were collected from superior cervical ganglionectomized (SCGX) and sham-treated rats at time intervals following surgical manipulation. Pineal noradrenaline (NA) levels were quantitated by a radioisotopic-enzyme technique, or the pineals were examined by histofluorescence or electron microscopic techniques. A significant decline in pineal NA content was observed by 12 hours with a virtual disappearance of NA by 24 hours following SCGX. The depletion of NA content correlated with the disappearance of synaptic vesicles and the appearance of generalized fine structural degeneration of the sympathetic nerve endings in the pineals. Then results indicate that less than one day is required to remove all of the potentially, functional neurotransmitter from the denervated pineal gland. These observations agree closely with the time course of degeneration of other sympathetic nerve terminals following SCGX.

Animals↗