Mammalian pineal function appears to be controlled primarily through the release of noradrenaline from the terminals of nerves whose cell bodies lie in the superior cervical ganglia This is the final segment of the following neural pathway: retina----retinohypothalamic projection----suprachiasmatic nuclei----paraventricular nuclei----intermediolateral cell column----superior cervical ganglia----nervi conarii----pineal gland Noradrenaline acts on pinealocytes through alpha- and beta-adrenoceptors in an atypical manner Beta-Adrenergic activation is an absolute requirement for the stimulation of both cyclic AMP and cyclic GMP production, and by itself produces a sixfold increase in the former and a twofold increase in the latter Alpha-Adrenergic activation potentiates the beta-adrenergic stimulation of cyclic AMP production 10-fold, and that of cyclic GMP production about 200-fold The mechanism of alpha- and beta-adrenergic interaction is being examined, and progress is being made in understanding the adrenergic control of cyclic AMP It appears that alpha-adrenergic agonists act through the alpha 1-subclass of adrenoceptors to stimulate phospholipid turnover and the production of a breakdown product of phosphatidylinositol, diacylglycerol This compound promotes the association of protein kinase C with membranes, which leads to the marked phosphorylation of one protein The precise identity of this protein remains a mystery This interaction leads to a larger cyclic AMP response but does not appear to be involved in the mechanism of potentiation of the cyclic GMP response Changes in chronic neural stimulation produce reciprocal changes in the magnitudes of cyclic AMP and cyclic GMP responses Chronic denervation results in a supersensitive cyclic AMP response and nearly complete disappearance of the cyclic GMP response This is termed 'see-saw' signal processing All the available evidence indicates that melatonin production is regulated by cyclic AMP This nucleotide not only increases the activity of serotonin N-acetyltransferase (more correctly called arylalkylamine N-acetyltransferase) but also stabilizes the enzyme and prevents its inactivation

Photoneural regulation of the mammalian pineal gland.

Rhythmic Transcription: The Molecular Basis of Circadian Melatonin Synthesis

✓ Since the discovery of melatonin approximately 25 years ago, there has been intense study regarding the details of the structure and function of the pineal gland. This work is reviewed, with particular emphasis on those aspects of importance to human physiology and disease.

The pineal gland: anatomy, physiology, and clinical significance

Lower vertebrates can detect UV light with the pineal complex independently of eyes. Electrophysiological studies, together with chromophore extraction analysis, have suggested that the underlying pigment in the lamprey pineal exhibits a bistable nature, that is, reversible photoreaction by UV and visible light, which is never achieved by known UV pigments. Here we addressed the molecular identification of the pineal UV receptor. Our results showed that the long-hypothesized pigment is a lamprey homologue of parapinopsin, which exhibits an absorption maximum at 370 nm, in the UV region. UV light causes cis-trans isomerization of its retinal2 chromophore, forming a stable photoproduct having an absorption maximum at 515 nm, in the green region. The photoproduct reverts to the original pigment upon visible light absorption, showing photoregeneration of the pigment. In situ hybridization showed that parapinopsin is selectively expressed in the cells located in the dorsal region of the pineal organ. We successfully obtained the hyperpolarizing responses with a maximum sensitivity of ≈380 nm from the photoreceptor cells at the dorsal region, in which the outer segment was clearly stained with anti-parapinopsin antibody. These results demonstrated that parapinopsin is the pineal UV pigment having photointerconvertible two stable states. The bistable nature of the parapinopsin can account for the photorecovery of the pineal UV sensitivity by background green light in the lamprey. Furthermore, we isolated the parapinopsin homologues from fish and frog pineal complexes that exhibit UV sensitivity, suggesting that parapinopsin is a common molecular basis for pineal UV reception in the vertebrate.

https://www.pnas.org/content/pnas/101/17/6687.full.pdf

Bistable UV pigment in the lamprey pineal

By means of immunocytochemistry retinal S-antigen is selectively demonstrated in retinal photoreceptor cells of the rat and in pinealocytes of the hedgehog, rat, gerbil and cat. Brain areas surrounding the pineal organ are immunonegative. The immunoreactive material is evenly distributed in the perikarya of the cells. Occasionally, inner segments of retinal photoreceptors and processes of pinealocytes are also stained. The outer segments of retinal photoreceptors display a strong immunoreaction. In both pinealocytes and retinal photoreceptors the intensity of the immunoreaction varied considerably among individual cells. The immunocytochemical demonstration of retinal S-antigen in mammalian pinealocytes indicates that these cells still bear characteristics of photoreceptors. This finding is in accord with the concept that mammalian pinealocytes are derived from pineal photoreceptor cells of poikilothermic vertebrates.

Immunocytochemical demonstration of retinal S-antigen in the pineal organ of four mammalian species.

The pineal organ is a derivative and integral component of the brain. In phylogeny it has changed from a 'third eye' capable of direct achromatic and/or chromatic responses to light to an endocrine gland influenced by visual stimuli from the retina. The outer segment of pineal photoreceptors contains a microspectrophotometrically detectable photopigment and an opsin-immunoreactive protein. Certain pinealocytes endowed with an outer segment display fluorophores of 5-HT/HTP and can be regarded as photoneuroendocrine cells. These photoneuroendocrine cells resemble cerebrospinal fluid-contacting neurons. The intrinsic circuitry (wiring diagram) of pineal photoreceptor organs has been only partly deciphered ; this holds true also for the neurotransmitters and synaptic patterns. Pineal photoreceptor organs are connected to the brain, i.e., to habenular, pretectal, thalamic, tegmental (reticular), and hypothalamic centers. The special anatomical and physiological features of the pineal organ enable it to translate photic information into neural and neuroendocrine responses.

A Oksche

Papers

Evolution of the pineal complex: correlation of structure and function.