Postsynaptic localization of the alpha receptor-mediated stimulation of phosphatidylinositol turnover in pineal gland

Smith, Thomas L.; Eichberg, Joseph; Hauser, George

doi:10.1016/0024-3205(79)90116-4

Cited by 82 publications

(29 citation statements)

References 15 publications

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“…However, in view of the wide occurrence of P-adrenergic control systems in the brain and else- (3,4,11) and that a-adrenergic agonists potentiate the p3-adrenergic stimulation ofcyclic AMP (unpublished data). According to this, 3-adrenergic activation is an absolute requirement for an increase in cyclic AMP, presumably reflecting the activation ofadenylate cyclase (27,28) It should be added that norepinephrine is known to stimulate phospholipid turnover in the pineal gland through an a1-adrenergic mechanism (30)(31)(32). Based on observations, in a number of tissues, which indicate that a-adrenergic regulatory systems may involve phospholipids, calcium, and calmodulin (33,34), we suspect that a similar mechanism could be involved in the effects described in this report.…”

mentioning

confidence: 99%

Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

Klein¹,

Sugden²,

Weller³

1983

Proc. Natl. Acad. Sci. U.S.A.

242

103

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The role played by postsynaptic et-adrenergic receptors in the stimulation of pineal N-acetyltransferase (EC 2.3.1.5) and [3H]melatonin production was investigated in the rat. In vivo studies indicated that phenylephrine, an a-adrenergic agonist, potentiated and prolonged the effects of isoproterenol, a P adrenergic agonist. Similar observations were made in organ culture with glands devoid of functional nerve endings. In addition, a combination of 1 FAM prazosin, an a1-adrenergic blocking agent, and 1 FM propranolol, a -adrenergic blocking agent, was many times more potent then either agent alone in blocking the stimulatory effects of norepinephrine on N-acetyltransferase activity and [3Hlmelatonin production. These findings establish that norepinephrine acting through ar-and (3-adrenergic receptors stimulates rat pineal N-acetyltransferase activity and, as a result, the production of melatonin. Apparently, (-adrenergic activation is an absolute requirement, and an et-adrenergic receptor mechanism potentiates -adrenergic activation. These findings are significant because they demonstrate a-adrenergic potentiation of (-adrenergic effects. In addition, they indicate that the widely held belief that melatonin production is regulated exclusively by a postsynaptic -adrenergic mechanism must be revised.A daily rhythm in circulating melatonin occurs in all mammals (1). In the rat this is generated by a large rhythm in the activity of pineal arylamine N-acetyltransferase (EC 2.3.1.5) (1-4), the enzyme that converts serotonin to the immediate precursor of melatonin, N-acetylserotonin.The activity of N-acetyltransferase is regulated by a neural circuit that stimulates the nocturnal release of norepinephrine from sympathetic nerves in the pineal gland (5)(6)(7)(8). Norepinephrine acts through an adrenergic mechanism to increase intracellular cyclic AMP (9, 10) which induces and activates Nacetyltransferase (3, 4), leading to an increase in melatonin production (11,12).It is now generally thought, based on a number of studies (11)(12)(13)(14)(15)(16)(17), that norepinephrine acts exclusively through postsynaptic /3-adrenergic receptors to increase cyclic AMP, N-acetyltransferase-activity, and melatonin production. We were surprised, therefore, by recent observations (unpublished data) which seem to indicate that norepinephrine increases pineal cyclic AMP through an action involving both a-and (3-adrenergic receptors. We found that a combination of isoproterenol (10 ,tM) and phenylephrine (10 ,uM) produced a stimulation at 10 min, of cyclic AMP and cyclic GMP equivalent to that produced by norepinephrine (10 ,uM) and that the effect of phenylephrine (10 ,uM) or isoproterenol (10 ,uM) alone was <20% of that produced by the combination of isoproterenol (10 UM) and phenylephrine (10 MM).This raised the obvious possibility that N-acetyltransferase activity and melatonin production are also regulated by both aand (3adrenergic receptors located on postsynaptic structures. We have studied this question and our results, pr...

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mentioning

confidence: 99%

Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

Klein¹,

Sugden²,

Weller³

1983

Proc. Natl. Acad. Sci. U.S.A.

242

103

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“…Dopamine, which has been shown to stimulate adenylate cyclase in carp retinal horizontal cells (32,34), has no effect on phosphoinositide metabolism. Likewise, norepinephrine, which is known to elicit a phosphoinositide response in other neural tissues (17,30), was not effective in producing a phosphoinositide response in the retina.…”

Section: Discussionmentioning

confidence: 93%

“…However, there are little data to support such a role, and it is now clear that the PI response is postsynaptic (8,30). Thus, neurotransmitter-stimulated phosphoinositide turnover is most likely associated with cellular activities other than transmitter release .…”

Section: Discussionmentioning

confidence: 99%

Inositol incorporation into phosphoinositides in retinal horizontal cells of Xenopus laevis: enhancement by acetylcholine, inhibition by glycine.

Anderson

Hollyfield

1984

The Journal of Cell Biology

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The absorption of light by photoreceptor cells leads to an increased incorporation of [2-3H]inositol into phosphoinositides of horizontal cells in the retina of Xenopus laevis in vitro. We have identified several retinal neurotransmitters that are involved in regulating this response. Incubation with glycine, the neurotransmitter of an interplexiform cell that has direct synaptic input onto horizontal cells, abolishes the light effect. This inhibition is reversed by preincubation with strychnine. Acetylcholine added to the culture medium enhances the incorporation of [2-3H]inositol into phosphoinositides in horizontal cells when retinas are incubated in the dark. This effect is inhibited by preincubation with atropine. However, atropine alone does not inhibit the light-enhanced incorporation of [2-3H]inositol into phosphoinositides in the retina. gamma-Aminobutyric acid, the neurotransmitter of retinal horizontal cells in X. laevis, as well as dopamine and norepinephrine, have no effect on the incorporation of [2-3H]inositol into phosphoinositides. These studies demonstrate that the light-enhanced incorporation of [2-3H]inositol into phosphoinositides of retinal horizontal cells is regulated by specific neurotransmitters, and that there are probably several synaptic inputs into horizontal cells which control this process.

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“…We can only refer to very weak evidence that associates cGMP with specific pineal functions. First, because the pineal cGMP and phosphatidylinositol appear to be regulated by a-adrenergic receptors (4,5,(18)(19)(20), one might suspect that cGMP is involved in producing the phosphatidylinositol effect. However, limited studies using dibutyryl cGMP (20), and the presence of the phosphatidylinositol response in denervated glands (18), suggest that this view is probably wrong.…”

Section: Discussionmentioning

confidence: 99%

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

Klein¹,

Auerbach²,

Weller³

1981

Proc. Natl. Acad. Sci. U.S.A.

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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.A major development in regulatory biology has been the identification and description of a wide variety of mechanisms that quantitatively modulate stimulus-response relationships. The best studied category is homologous desensitization, seen almost universally in adrenergic-cyclic AMP (cAMP) systems and many other neural and hormonal regulatory processes (1). Forms of heterologous sensitization and desensitization have also been identified (1-3).We now describe another form of stimulus-response modulation, homologous sensitization, which controls the magnitude of the adrenergic stimulation of pineal cyclic GMP (cGMP). This response, apparently mediated by a-adrenergic receptors (4, 5), had been thought to occur primarily in the nerve endings in pineal glands (4-7). Results presented here prove that this interpretation is not correct and that the cGMP response occurs in pineal cells. We find that maximal responsiveness is maintained on a day-to-day basis by the normal daily pattern ofneural stimulation; chronic deprivation ofstimulation severely attenuates responsiveness.This discovery is especially noteworthy because neural stimulation has the opposite effect on the pineal 3-adrenergiccAMP relationship (8-10), i.e., a decrease in sensitivity. Concurrent sensitization and desensitization of these responses to (-)-norepinephrine, which we term seesaw signal processing, has intriguing implications, especially regarding the control of multiple cell functions and the process of neural transduction.

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Postsynaptic localization of the alpha receptor-mediated stimulation of phosphatidylinositol turnover in pineal gland

Cited by 82 publications

References 15 publications

Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

Postsynaptic alpha-adrenergic receptors potentiate the beta-adrenergic stimulation of pineal serotonin N-acetyltransferase.

Inositol incorporation into phosphoinositides in retinal horizontal cells of Xenopus laevis: enhancement by acetylcholine, inhibition by glycine.

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

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