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Biomedical subjects

D C Klein

Publications and source records attributed to D C Klein.

At least 163 records · Page 9Linked to original sources
PubMed1983

Regulation of rat pineal hydroxyindole-O-methyltransferase in neonatal and adult rats.

The relative importance of neural, and some nonneural, mechanisms in the control of pineal hydroxyindole-O-methyltransferase (HIOMT) activity during development and in the adult rat was studied. In neonatal rats, guanethidine-treatment, bilateral superior cervical ganglionectomy (SCGX), or exposure to constant light did not prevent the initial appearance of HIOMT activity, indicating that neural stimulation of the gland is not essential for the development of HIOMT activity. In adult rats, decentralization or removal of the SCG led to a slow fall in HIOMT activity, to about 30% of control activity, indicating that the enzyme is largely under neural control. Additionally, adrenalectomy or hypophysectomy had no effect on HIOMT activity, refuting the suggestion that adrenal and/or gonadal steroids are of major importance in the regulation of this enzyme. The fall in activity of the enzyme after SCGX or exposure to constant light probably does not represent a shift in the Km of the enzyme nor the selective disappearance of a distinct molecular species. Similar changes in HIOMT activity and cyclic GMP responsiveness occur in response to alterations in the length of the daily dark period, adding further evidence to our earlier speculation that there may be a functional relationship between these two.

Acetylserotonin O-Methyltransferase↗
PubMed1983

Beta-adrenergic receptor control of rat pineal hydroxyindole-O-methyltransferase.

The nature of the postsynaptic adrenergic receptor on rat pinealocytes which controls hydroxyindole-O-methyltransferase (HIOMT) activity was studied. This enzyme is involved in the synthesis of the pineal hormone melatonin. Adrenergic drugs were administered continuously for a 7-day period to rats in which neural stimulation of the pineal gland was blocked by either superior cervical ganglionectomy or exposure to constant light. l-Isoproterenol, a beta-adrenergic agonist, prevented the fall in enzyme activity that occurs when neural stimulation is interrupted; d-isoproterenol was ineffective. The potency order of different adrenergic agonists was d,l-isoproterenol greater than l-norepinephrine greater than l-epinephrine. Terbutaline, a selective beta 2-adrenergic agonist, was ineffective. The selective alpha 1-adrenergic agonists phenylephrine and methoxamine and the alpha 2-agonist clonidine were also ineffective. High doses of the beta-adrenergic blocker propranolol antagonized the effect of isoproterenol and caused a fall in HIOMT activity in normal rats housed under normal diurnal lighting. This in vivo evidence is consistent with the hypothesis that the neural control of pineal HIOMT is mediated via a beta-adrenergic receptor.

Acetylserotonin O-Methyltransferase↗
PubMed1983

Reciprocal day/night relationship between serotonin oxidation and N-acetylation products in the rat pineal gland.

Pineal tryptophan, serotonin [5-hydroxytryptamine (5-HT)], N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxytryptophol, and 5-methoxyindoleacetic acid were measured by high pressure liquid chromatography with electrochemical detection. A complete analysis required less than the equivalent of two rat pineal glands. Samples were obtained at eight time points. A reciprocal physiological relationship was found between oxidation and N-acetylation products of 5-HT. 5-HT and the oxidation products 5-hydroxyindoleacetic acid, 5-hydroxytryptophol, 5-methoxytryptophol, and 5-methoxyindoleacetic acid decreased at night, when the N-acetylation products N-acetylserotonin and melatonin increased. These observations are consistent with the hypothesis that circadian changes in the N-acetylation of 5-HT by indoleamine N-acetyltransferase is the major factor controlling circadian changes in the amounts of 5-HT, and 5-HT oxidation and N-acetylation products in the rat pineal gland.

Acetylation↗
PubMed1982

Activation of pineal acetyl coenzyme A hydrolase by disulfide peptides.

Incubation of pineal acetyl-CoA hydrolase preparations with disulfide peptides activates the enzyme. Activation of somatostatin, the most potent peptide tested, is enhanced at higher pH, indicating that disulfide exchange is probably involved. This interpretation is supported by the observation that activation is reversed by dithiothreitol treatment. The order of potency is somatostatin = [Tyr1]somatostatin greater than or equal to Tyr-somatostatin greater than vasopressin = pressinoic acid = [Arg8]vasotocin greater than oxytocin. Insulin, insulin A, insulin B, and [Asu1,6, Arg8]vasopressin were ineffective. This order of potency is distinctly different from that for the inactivation of pineal N-acetyltransferase (Namboodiri, M. A. A., Favilla, J., and Klein, D. C. (1981) Science 213, 571-573) by these peptides. Examination of the primary structure of the peptides reveals that the above order of potency is consistent with the predictions of the nearest neighbor model as applied to the disulfide group.

Acetyl-CoA Hydrolase↗
PubMed1981

The effects of environmental lighting on the daily melatonin rhythm in primate cerebrospinal fluid.

The effects of alterations in environmental lighting on the daily rhythm in cerebrospinal fluid concentrations of melatonin were studied in the rhesus monkey. It was found that acute exposure to darkness during the day did not markedly increase normally low daytime CSF melatonin levels, that light suppressed the normally high CSF melatonin values at night, and that 12-h phase shifts in the diurnal lighting cycle caused 12-h phase shifts in the rhythm. The daily rhythm persisted for 6.5 days of study in constant darkness and the phase of the rhythm was not affected in constant darkness by a 12-h phase shift in the daily delivery of food and daily care of the animals. These results support the notion that the melatonin rhythm in this primate species is endogenous in nature, and that light can act to both coordinate the rhythm to the 24-h day and to acutely suppress melatonin production.

Animals↗
PubMed1981

Biosynthesis of biopterin: adrenergic cyclic adenosine monophosphate-dependent inhibition in the pineal gland.

Pineal glands in organ culture synthesize and release biopterin and are able to maintain concentrations of biopterin occurring in vivo for up to 54 hours in vitro. The intracellular biopterin content is reduced 50 percent by treatment with l-norepinephrine or cyclic adenosine monophosphate derivatives, but not by d-norepinephrine. This is an indication that biopterin levels are regulated by an adrenergic cyclic adenosine monophosphate-dependent mechanism. The decline in tissue biopterin content, produced mainly by inhibited of biosynthesis, is maximal at 6 hours and is not associated with either an increase in biopterin release or a shift in the reduction state of the biopterin.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Pineal N-acetyltransferase is inactivated by disulfide-containing peptides: insulin is the most potent.

Pineal N-acetyltransferase can be inactivated in broken cell preparations by cystamine through a mechanism of thiol-disulfide exchange. Some, but not all, disulfide-containing peptides can inactivate this enzyme; the most potent inactivator is insulin. These findings suggest that a disulfide-containing peptide with high reactivity toward N-acetyltransferase may participate in the intracellular regulation of this enzyme.

Acetyltransferases↗
PubMed1981

Seesaw signal processing in pineal cells: homologous sensitization of adrenergic stimulation of cyclic GMP accompanies homologous desensitization of beta-adrenergic stimulation of cyclic AMP.

Studies of the adrenergic regulation of cyclic GMP in the pineal gland show that (-)-norepinephrine stimulates cyclic GMP primarily in pineal cells, rather than in nerve endings as previously thought. The response exhibits the interesting and unusual characteristic of homologous sensitization: It is maintained by neural stimulation and disappears gradually as a consequence of depressed neural stimulation, due to denervation or decentralization of the superior cervical ganglia or to constant light. The response is restored in intact animals that had been in a constant-light environment when they are returned to a normal light cycle and in ganglionectomized animals by norepinephrine treatment. These findings are especially interesting because the pineal adrenergic--cyclic AMP stimulus--response system exhibits homologous desensitization. The occurrence of homologous sensitization of a cyclic GMP response and desensitization of a cyclic AMP response, which we term seesaw signal processing, in the same tissue or cell has intriguing implications. It provides a mechanism through which the qualitative nature of a multicomponent response can be modified. Such a mechanism could play a role in signal processing by neural or neuroendocrine tissues that release two or more extracellular messages.

Animals↗
PubMed1981

Daily rhythms in cortisol and melatonin in primate cerebrospinal fluid. Effects of constant light and dark.

Cerebrospinal fluid was continuously collected from the cisternal-cervical subarachnoid space of chair-restrained rhesus monkeys. The concentrations of melatonin and cortisol were measured in the cerebrospinal fluid. Under diurnal lighting (light:dark, 12:12 h) melatonin concentrations were elevated during darkness and low during illumination. The melatonin rhythm persisted in constant darkness but was suppressed in constant illumination. Under diurnal lighting, cortisol concentrations were elevated in the early portion of the light period. This daily rhythmicicty of cortisol secretion was not altered by constant illumination or constant darkness. The differential response of the two hormones to constant light suggest that the daily fluctuation of melatonin secretion was not responsible for the daily rhythmicity of cortisol secretion in the rhesus monkey.

Animals↗
PubMed1981

Neonatal rat pinealocytes: typical and atypical characteristics of [125I]iodohydroxybenzylpindolol binding and adenosine 3',5'-monophosphate accumulation.

Techniques are described which make it possible to study beta-adrenergic receptors on intact neuroendocrine cells. Receptors were characterized on neonatal pinealocytes using the radioligand [125I]iodohydroxybenzylpindolol ([125I]IHYP). Specific binding of [125I]IHYP, which is 4-fold greater than nonspecific binding, is concentration and temperature dependent, reversible, and saturable. [125I]IHYP binds noncooperatively (Kd = 35 pM), and Scatchard analysis indicates that only a single class of receptor sites for [125I]IHYP is present. Under the conditions used, it appears that there are about 12,000 +/- 1,100 sites/cell. Inhibition of specific [125I]IHYP binding by beta-adrenergic agonists and antagonists is stereospecific, and the relative potency of agonists is characteristic of binding to beta-adrenergic receptors. Analysis of adrenergic stimulation of intracellular cAMP accumulation indicates that similar half-maximal concentrations of antagonists inhibit [125I]IHYP binding and adrenergically stimulated cAMP accumulation. In contrast, beta-adrenergic agonists are considerably more potent in stimulating cAMP than in inhibiting [125I]IHYP binding. Unexpected differences, not previously reportd, were found in the shapes of the cAMP accumulation dose-response curves of norepinephrine and isoproterenol. The relative potencies of these two agonists appear to be partially concentration dependent. This raises the possibility that there may be distinct differences in the intrinsic effects of these compounds on the regulation of intracellular cAMP accumulation in pinealocytes. (Endocrinology 108: 559, 1981)

Alprenolol↗
PubMed1981

Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey.

The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibited a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.

Amino Acids↗
PubMed1980

Evidence of inactivation of pineal indoleamine N-acetyltransferase by protein thiol:disulfide exchange.

Pineal indoleamine N-acetyltransferase activity in homogenates is rapidly reduced at pH 6.8 by treatment with cystamine or arginine vasotocin. Other disulfides including glutathione disulfide, penicillamine disulfide, and N,N'-diacetylcystamine are either ineffective or less effective. The diamine analogous to cystamine, diaminohexane, is also ineffective. Inactivation by cystamine is accelerated at higher pH and is temperature- and time-dependent. It was also found that cystamine treatment inactivated N-acetyltransferase in intact pineal cells. Treatment with dithiothreitol reactivated the cystamine- or arginine vasotocin-inactivated enzyme formed in broken cell preparations and the cystamine-inactivated enzyme formed in intact cells. These observations indicate that pineal N-acetyltransferase can be inactivated by protein thiol:disulfide exchange; further research is required to ascertain whether this mechanism is of physiological significance.

Acetyltransferases↗
PubMed1980

Taurine release from the pineal-gland is stimulated via a beta-adrenergic mechanism.

Pineal glands were prelabeled in organ culture with [14C]taurine, and then treated with biogenic amines. The rate of release of [14C]taurine was rapidly elevated by low concentrations of norepinephrine, apparently acting through a beta-adrenergic mechanism. The release was probably not due to a nonspecific change in membrane permeability, as a comparable release was not seen with [14C]glycine and [14C]alpha-aminoisobutyric acid. These findings suggest that the release of taurine may be related to or a reflection of the early events in adrenergic activation of the pineal gland, such as hyperpolarization of pinealocytes. The released taurine might also have an extracellular role as it has been recently shown that extracellular taurine can interact with pineal beta-adrenergic receptors to stimulate melatonin production. Thus, the released taurine could possibly act as an extracellular feedback messenger.

Acetyltransferases↗