Role of proline in the imprinting developed by dipeptides — in Tetrahymena Possible role in hormone evolution

The effects of proline and serine dipeptides containing phenylalanine, alanine and leucine on the behaviour of receptors of Tetrahymena were investigated. Only proline-containing dipeptides were able to develop positive imprinting, and the activity depended on which other amino acid was present in the dipeptide. In contrast to the positive imprinting effect of the dipeptides Pro-Phe and Pro-Ala, the dipeptide Pro-Pro and Pro-Leu caused negative imprinting. Serine dipeptides produced negative imprinting in all cases. The possible importance of proline in the evolution of hormone specificity is discussed.     

Serotonin-stimulated protein phosphorylation in aortic smooth muscle cells

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.     

Effect of insulin on the glucose uptake of protozoa.

Insulin stimulates the glucose uptake of Tetrahymena pyriformis. This shows the presence of insulin receptors in Tetrahymena, consequently receptors may be present in a level of phylogenesis, where the natural contact between the given hormone and the cell is unnecessary and impossible.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives.

Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase of Pseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

Comparative study of the sensitivity of acetylcholinesterases and cholinesterases from animal and bacterial sources to inhibition by serotonin and its derivatives

Summary Serotonin was found to inhibit human erythrocyte and electric-eel acetylcholinesterase activities. The serotonin amino group, free of negative charges in its vicinity and its hydroxyl group, were important for the inhibition. Serotonin precursors and several related compounds had little or no effect. Human plasma cholinesterase was also inhibited by serotonin and tryptamine. In contrast to these animal enzymes, the cholinesterase ofPseudomonas aeruginosa was refractory to serotonin and its derivatives under the same experimental conditions.     

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.     

Intrinsic and extrinsic neural and neurohumoral control of the decapod heart

The intra-cardiac nervous system of the decapod heart is composed of large and small ganglionic cells (LGCs and SGCs) and axons of extrinsic cardio-acceleratory and-inhibitory neurons (CAs and CIs). Candidate neurotransmitters for the neurons have been determined by pharmacological, cytochemical and immunocytochemical tests. SGCs may be cholinergic, LGCs and CAs are probably dopaminergic, and CIs are GABAergic. Serotonin and octopamine were cardio-excitatory neuromodulators of the heart. Proctolin, crustacean cardio-active peptide (CCAP), red pigment concentrating hormone (RPCH), and FMRFamide also had modulatory actions on the heart. Proctolin was the most potent peptide, which acted primary on the cardiac ganglion. Insect adipokinetic hormones had little effect on the heart.     

Presence of benzodiazepine binding sites (receptors) and amplification thereof by imprinting in Tetrahymena

Live Tetrahymena cells bound 3H-diazepam specifically, as demonstrated by autoradiographic evidence of displacement of about 25% of labeled diazepam in the presence of a 1000-fold amount of cold diazepam. The 3H-diazepam bound to membrane preparations isolated from untreated (control) cells was not displaced by cold diazepam, whereas cells involved in primary interaction (imprinting) with diazepam showed amplification and specificity of diazepam binding in both in vivo (cell suspension) and in vitro (pellicle) systems, as well as displacement of bound label in the presence of 1000-fold cold diazepam. It appears that diazepam induced imprinting and, consequently, also the formation of specific receptors in Tetrahymena.     

Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.Received 16 June 2004; received after revision 9 September 2004; accepted 23 September 2004     

EGF receptor induction and insulin-EGF overlap in Tetrahymena

Offspring generations of Tetrahymena pretreated (imprinted) with insulin showed a greater binding capacity for the hormone than offspring of untreated ones. The epidermal growth factor (EGF) imprinted for insulin to a greater degree than insulin itself, and vice versa: insulin imprinted for EGF more efficiently than EGF itself. These phenomena can be explained by the overlap of insulin and EGF on one another's receptors in Tetrahymena.     

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     

Is feminine differentiation of the brain hormonally determined?

Summary The androgen insensitive, genetically male rat pseudohermaphrodite displays neither masculine or feminine sexual behavior when primed with the appropriate sex hormones. although in the absence of androgen imprinting the animal develops anatomically as female, our results suggest that feminine differentiation of the brain requires active imprinting by perinatal hormone(s), possibly adrenal progesterone.The research was partially supported by a grant from the Rockefeller Foundation.A. S. Goldman is a U.S.P.H.S. Career Development Awardee (No. HD-13,628).     

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

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.     

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.     

Alzheimer’s disease: the impact of age-related changes in reproductive hormones

Receptors for hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function are expressed throughout the brain, and in particular the limbic system. The most studied of these hormones, the sex steroids, contain receptors throughout the brain, and numerous estrogenic, progestrogenic and androgenic effects have been reported in the brain related to development, maintenance and cognitive functions. Although less studied, receptors for gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and activins also are found throughout the limbic system on a number of cell types, and they too transduce signals from circulating hormones as demonstrated by their multiple effects on the growth, development, maintenance and function of the brain. This review highlights the point that because of the feedback loops within the HPG axis, it is difficult to ascribe structural and functional changes during development, adulthood and senescence to a single HPG hormone, since a change in the concentration of any hormone in the axis will modulate hormone concentrations and/or receptor expression patterns for all other members of the axis. The most studied of these situations is the change in serum and neuronal concentrations of HPG hormones associated with menopause/andropause. Dysregulation of the HPG axis at this time results in increases in the concentrations of serum GnRH, gonadotropins and activins, decreases in the serum concentrations of sex steroid and inhibin, and increases in GnRH and LH receptor expression. Such changes would result in significantly altered neuronal signaling, with the final result being that there is i.e. increased neuronal GnRH, LH and activin signaling, but decreased sex steroid signaling. Therefore, loss of cognitive function during senescence, typically ascribed to sex steroids, may also result from increased signaling via GnRH, LH or activin receptors. Future studies will be required to differentiate which hormones of the HPG axis regulate/maintain cognitive function. This introductory review highlights the importance of the identification of HPG hormone neuronal receptors and the potential of serum HPG hormones to transduce signals to regulate brain structure and function during development and adult life.     

Innervation and control of the heart of a gastropod,Rapana

Summary The innervation and control of the heart of a prosobranch mollusc,Rapana thomasiana, were studied. Acetylcholine was found to be an inhibitory neurotransmitter. Both serotonin and FMRFamide (Phe-Met-Arg-Phe-NH₂) showed excitatory effects on the heart; FMRFamide had greater inotropic and more regulatory chronotropic effects than serotonin. The effects of serotonin were blocked by methysergide, while the effects of FMRFamide and of stimulating the excitatory cardiac nerves were not blocked. Stimulation of circumesophageal ganglia elicited a slow enhancement of heart beat together with body movement. This enhancement was blocked by methysergide. Serotonin was considered to act at the heart as a local neurohormone. Although the mechanism of action of FMRFamide is still not yet clarified, it is possible that FMRFamide plays a physiological role as a cardioregulatory substance, as indicated by the physiological and histological findings.     

Regulation of B and T cell development by anterior pituitary hormones

Hormones produced by the anterior pituitary gland have been implicated in the regulation of primary lymphocyte development. In order to identify endocrine factors involved in that process, several strains of mice with genetic defects resulting in a selective impairment in the production of one or more anterior pituitary-derived hormones have been analysed. This study has resulted in the classification of endocrine hormones into the following four categories (i) hormones such as prolactin with no apparent effects on primary lymphopoiesis; (ii) anabolic hormones such as growth hormone and insulin-like growth factor-I whose stimulatory effects on primary lymphopoiesis are non-lineage-specific and related to their actions as systemic mediators of growth and/or differentiation; (iii) hormones such as thyroid hormones that have an obligate role in primary B lymphopoiesis; and (iv) hormones such as oestrogens that act as negative regulators of lymphopoiesis.     

Immunologic properties of ovine chorionic somatomammotropin]

Immunological properties of ovine chorionic somatomammotropin (OSC) are studied immunodiffusion, radio-immunoassays and by comparative studies of serum hormonal changes during pregnancy. OCS shows no immunological cross-reaction with ovine prolacin, ovine, bovine and human growth hormone and human placental lactogen. Structural analogies of these hormones are discussed.     

Nerve growth factor selectively stimulates the degradation of chondromucoprotein in the embryonic cartilage in vitro.

Nerve growth factor specifically stimulates the degradation of chondromucoprotein in the chick embryonic cartilage cultivated in vitro, with little effect on chondromucoprotein, RNA, DNA and protein synthesis.     

Serotonin metabolism in chronic alcoholism (author's transl)

Serotonin was determined in platelets of 47 patients with alcoholism during the state of withdrawal as well as in a group of healthy persons. The results show that serotonin values were significantly lower in the group of patients with alcoholism as compared with the control group of healthy persons.