Differential effects of the serotonin receptors on cultured rat cerebral cortical neurons

Effects of serotonin (5-HT) on cerebral cortical neurons were examined by patch clamp techniques. 5-HT produced a variety of responses such as outward (19/73 patches/neurons), slow inward (15/73 patches/neurons), fast inward (8/73 patches/neurons), and mixed currents (initially fast inward deflection followed by an outward response: 2/73 patches/neurons), with a latency of 12 sec, 15 sec, 0 sec, and 0 sec respectively, at a holding potential of −60 mV in whole-cell patches. The fast inward currents were again evoked by a selective 5-HT3 receptor agonist, 1-(m-chlorophenyl)-biguanide hydrochloride (CPBG). In the cell-attached patch clamp configuration, 5-HT inside the patch pipette elicited single channel currents with slope conductances of 42 pS and 132 pS (4/42 patches/neurons). CPBG inside the patch pipette evoked inward single channel currents with a lower slope conductance of 41 pS (3/23 patches/neurons). In contrast, application of 5-HT or a 5-HT₂ receptor agonist, α-methyl-5-hydroxytryptamine-maleate, outside the patch pipette induced outward single channel currents with a major slope conductance of 140 pS (8/30 patches/neurons) or 135 pS (6/20 patches/neurons), respectively. These results indicate that the outward and fast inward currents may be mediated respectively by the 5-HT₂ receptor, which is coupled to a G-protein, and by the 5-HT₃ receptor, which contains the non-selective cation channel, and that the mixed type may be caused by both the 5-HT₂ and 5-HT₃ receptors. Received 27 September 1996; received after revision 4 November 1996; accepted 7 November 1996     

Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives

Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases. Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007     

Morphological effects of serotonin and ketanserin on embryonic chick skin in vitro

Summary Cell and organotypical cultures are used to study the direct effect of serotonin and of ketanserin, a serotonin antagonist, on dermal and epidermal cells of embryonic chick skin. Ketanserin stimulates the increase in cell number and inhibits the differentiation, whereas serotonin stimulates differentiation and inhibits the increase in cell number.     

Tetanus intoxication causes an increment of serotonin in the central nervous system

Summary Mice injected with tetanus toxin (TTx) showed an increase of 5-hydroxytryptamine (serotonin, 5-HT) levels in the central nervous system. The increment was not uniform thoughout the central nervous system. Particularly significant were the 25% and 80% increases observed, respectively, in whole brain and spinal cord. The levels of dopamine and norepinephrine remained unchanged. The subsequent studies of 5-HT turnover revealed a synthesis rate in the tetanic animals that was almost double that of controls. The degradation rate of the amine as well as the levels of 5-hydroxyindolacetic acid were unaffected.     

Serotonin-stimulated protein phosphorylation in aortic smooth muscle cells

Summary The effects of serotonin on the formation of inositol phosphates and protein phosphorylation were examined in cultured smooth muscle cells. Serotonin stimulated the formation of [³H]inositol monophosphate, [³H]inositol bisphosphate and [³H]inositol trisphosphate. This effect was prevented by 5-HT₂ specific antagonist, 6-methyl-1-(1-methylethyl)ergoline-8-carboxylic acid, 2-hydroxy-1-methylpropyl ester [Z]-2-butenedioate (LY53857). Serotonin stimulated the phosphorylation of many polypeptides, among which a 20 kDa polypeptide was the most prominent. The phosphorylation was also inhibited by LY53857. LY53857 alone produced no effects on protein phosphorylation. The 20 kDa polypeptides were also phosphorylated by the addition of 12-O-tetradecanoylphorbol-13-acetate. These results suggest that serotonin stimulates protein phosphorylation through 5-HT₂ receptors and possibly activates protein kinase C in intact vascular smooth muscle cells.Part of the data contained in this paper was presented at the 74th local meeting of the Japanese Society of Pharmacology at Kanagawa.     

Circulating serotonin in vertebrates

The role of circulating serotonin is unclear and whether or not serotonin is present in the blood of non-mammalian species is not known. This study provides the first evidence for the presence of serotonin in thrombocytes of birds and three reptilian species, the endothermic leatherback sea turtle, the green sea turtle and the partially endothermic American alligator. Thrombocytes from a fresh water turtle, American bullfrog, Yellowfin tuna, and Chinook salmon did not contain serotonin. Serotonin is a vasoactive substance that regulates skin blood flow, a major mechanism for endothermic body temperature regulation, which could explain why circulating serotonin is present in warm-blooded species. The temperature sensitivity of human blood platelets with concomitant changes in serotonin content further supports a link between circulating serotonin and thermoregulation. Phylogenetic comparison of the presence of circulating serotonin indicated an evolutionary divergence within reptilian species that might coincide with the emergence of endothermy.Received 2 April 2005; received after revision 15 May 2005; accepted 15 June 2005     

Indoleamines and the UV-light-sensitive photoperiodic responses of the melanocyte network: a biological calendar?

The pineal, serotoninergic and pigmented neurons are associated with light-dependent sleep/arousal, serving as a biological clock with a circadian rhythm. This rhythm is maintained by melatonin which serves to recognise the dark phase. The neural network that responds to seasonal variations in day/night length has not been identified. The present study demonstrates that melanocytes in human skin respond to changes in the duration of UV exposure, and can serve as a biological calendar. These responses are mediated by two indoleamines, serotonin and melatonin. Higher melatonin levels correspond to long nights and long days (short UV pulse), while high serotonin levels in the presence of melatonin reflect short nights and long days (long UV exposure). This response recapitulates the sleep/arousal patterns in animals exposed to large variations in day/night cycle that cause changes in coat colour from pure white in winter to complete repigmentation in summer.     

Presence in and effects of pineal indoleamines at very low level of phylogeny

The unicellular organism Tetrahymena contains serotonin and is able to take up the hormone from its mileiu. The serotonin content of the cell changes as a function of the presence of foreign exogenous hormones. This indicates a possible role of serotonin as a chemical mediator. Exogenous serotonin stimulates the RNA synthesis of Tetrahymena, and it was the only one among the hormones studied which kept the RNA level durably high. Serotonin stimulates phagocytosis and growth of Tetrahymena, and its precursors also stimulate growth. Serotonin can imprint Tetrahymena, and as a consequence of this the effect of the hormone increases in the case of further encounters. Treatment with serotonin-related molecules soon after imprinting can reduce the effect of imprinting. Melatonin can contract the pigment cells of Planaria; however, its precursors serotonin and tryptamine can do this more intensely. Both melatonin and serotonin can influenc the regeneration of Planaria, with effects which differ when different phenomena are studied. Evolutionary theories are discussed.