Marvin R. Brown

Bio: Marvin R. Brown is an academic researcher from University of California, San Diego. The author has contributed to research in topics: Somatostatin & Bombesin. The author has an hindex of 64, co-authored 167 publications receiving 12434 citations. Previous affiliations of Marvin R. Brown include Hammersmith Hospital & Salk Institute for Biological Studies.

Corticotropin-Releasing Factor: Actions on the Sympathetic Nervous System and Metabolism*

Abstract: Corticotropin-releasing factor (CRF) injected into the brains of rats produces hyperglycemia and an increase in plasma concentrations of glucagon, epinephrine, and norepinephrine. Neither hypophysectomy nor adrenalectomy prevents CRF-induced hyperglycemia. However, a role of adrenal epinephrine release in mediating CRF-induced hyperglycemia is supported by the finding that the central nervous system-selective somatostatin analog, desAA1,2,4,5,12,13-[D-Trp8]somatostatin, totally prevents the elevation of plasma epinephrine and suppresses the rise of plasma glucose but does not alter the increase in plasma norepinephrine induced by CRF. Pretreatment with the ganglionic blocker chlorisondamine completely prevents the CRF-induced rises in plasma glucose, epinephrine, and norepinephrine. These results demonstrate that CRF acts within the brain to stimulate sympathetic outflow, which results in the development of hyperglycemia. In contrast to other peptides that act within the central nervous system, e.g. bombe...

Bombesin-like immunoreactivity in the lung.

Abstract: THE first suggestion that the lung contained endocrine cells was made by Feyrter1 when introducing the concept of a diffuse endocrine or paracrine system, composed of epithelial ‘clear cells’. The presence of argyrophil cells in human and other mammalian lungs was later confirmed2,3 and it was shown that some of these cells contained amines, demonstrated by argent-affinity, formaldehyde-induced fluorescence (FIF), and the possession of neurosecretory type granules. They have variously been termed Feyrter cells4, Kultschitzky cells5, argy-rophil-fluorescent-granulated or AFG cells6, enteroch-romaffin-like cells7, neurosecretory cells8, pulmonary argyrophil cells9, endocrine or endocrine-like cells10,11, and possess APUD cell characteristics10–13. Endocrine cells are present within the bronchial and bronchiolar epithelium both as single elements and as groups of cells. Groups of innervated, endocrine-like cells termed neuroepithelial bodies have been demonstrated4. Some pulmonary endocrine cells contain 5-hydroxytryptamine10,14 and possibly other amines, but no peptide product has yet been identified in them. Said15 has proposed that the lung may produce a vasoactive peptide and it has subsequently been shown that the lung produces an angiotensin II-like peptide16,17 and two vasoactive peptides18, although the cellular origin of these peptides has not been established. Three major types of endocrine cell have been identified in human fetal lung (types 1, 2 and 3), a distinction based largely on the morphology of their secretory granules which are 110–200 nm in diameter12. Granules in the type-2 cell of the lung resemble those in P cells of the gut and pancreas19. The P-cell product has not been identified but it may be a bombesin-like peptide20. Bombesin is a tetra-decapeptide isolated from frog skin21 having a wide range of actions on the mammalian gastrointestinal tract and vasculature22. The similarity between P cells of the gut and certain granulated cells of the lung suggested that a bombesin-like peptide might be present in the human lung, and we report here the presence of bombesin-like immunoreactivity in human fetal and neonatal lung.

STIMULATION IN VIVO OF THE SECRETION OF PROLACTIN AND GROWTH HORMONE BY β-ENDORPHIN

Abstract: Morphine sulfate (MS) and the opioid peptide beta-endorphin beta-LPH-(61-91) stimulate prolactin and growth hormone release in steroid-primed and non-treated male rats when injected intravenously or intracisternally. On a molar basis beta-endorphin is at least 20 times more potent than MS, whereas Met5-enkephalin (beta-LPH-(61-65)) and alpha-endorphin (beta-LPH-(61-76)) are devoid of activity at the dose injected (300 mug). The in vivo stimulatory effects of beta-endorphin on prolactin secretion are reversed by the opiate antagonist naloxone. The absence of in vitro effect of MS and beta-endorphin on prolactin and growth hormone secretion by cultured rat pituitary cells suggest that they have a central nervous system site of action.

Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide.

Abstract: Alternative splicing of RNA transcripts from the calcitonin gene produces mRNAs that encode different polypeptides. While the mRNA encoding calcitonin predominates in thyroidal 'C' cells, calcitonin gene-related peptide (CGRP) mRNA appears to be the major mRNA component in non-thyroid tissue, including brain. The predicted peptide arising from translation of CGRP mRNA has now been identified immunocytochemically throughout the central and peripheral nervous systems. CGRP, a 37-residue peptide, is distributed in brain pathways subserving sensory, motor and autonomic functions. We report here that CGRP acts in the central nervous system to stimulate selectively noradrenergic sympathetic outflow.

Chemical and Biological Characterization of Corticotropin Releasing Factor

Abstract: Publisher Summary Hypothalamus liberates a substance into the hypophysial portal blood that stimulates the adrenocorticotrophic hormone (ACTH) activity of the pituitary. This chapter discusses the chemical and biological characterization of this corticotropin releasing factor (CRF). Several known naturally occurring substances including vasopressin, oxytocin, norepinephrine, epinephrine, and angiotensin II are found to stimulate ACTH secretion. Partially purified preparations of CRF stimulates the secretion of a number of peptides derived from the proopiomelanocortin (POMC) precursor—including the opioid peptide, β-endorphin. The chapter explains that CRF is likely to be distributed outside of the hypothalamus and possess extra hypophysiotropic actions. In vitro systems are vulnerable to non specific secretagogs in extracts including myelin basic protein, histones, potassium ion, and the components of various buffers and solvents. Ovine CRF is homologous with several known peptides including sauvagine and urotensin I. CRF also shows some homology with calmodulin and with angiotensinogen. The tetrapeptide Phe-His-Leu-Leu is common to both angiotensinogen and CRF and is the site in angiotensinogen of renin and converting enzyme cleavage. The chapter concludes with the evidence that supports CRF or a closely related peptide in the neuroregulation of the pituitary corticotropic cells.

How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions.

Abstract: The secretion of glucocorticoids (GCs) is a classic endocrine response to stress. Despite that, it remains controversial as to what purpose GCs serve at such times. One view, stretching back to the time of Hans Selye, posits that GCs help mediate the ongoing or pending stress response, either via basal levels of GCs permitting other facets of the stress response to emerge efficaciously, and/or by stress levels of GCs actively stimulating the stress response. In contrast, a revisionist viewpoint posits that GCs suppress the stress response, preventing it from being pathologically overactivated. In this review, we consider recent findings regarding GC action and, based on them, generate criteria for determining whether a particular GC action permits, stimulates, or suppresses an ongoing stressresponse or, as an additional category, is preparative for a subsequent stressor. We apply these GC actions to the realms of cardiovascular function, fluid volume and hemorrhage, immunity and inflammation, metabolism, neurobiology, and reproductive physiology. We find that GC actions fall into markedly different categories, depending on the physiological endpoint in question, with evidence for mediating effects in some cases, and suppressive or preparative in others. We then attempt to assimilate these heterogeneous GC actions into a physiological whole. (Endocrine Reviews 21: 55‐ 89, 2000)

Acute stressors and cortisol responses: a theoretical integration and synthesis of laboratory research.

Abstract: This meta-analysis reviews 208 laboratory studies of acute psychological stressors and tests a theoretical model delineating conditions capable of eliciting cortisol responses. Psychological stressors increased cortisol levels; however, effects varied widely across tasks. Consistent with the theoretical model, motivated performance tasks elicited cortisol responses if they were uncontrollable or characterized by social-evaluative threat (task performance could be negatively judged by others), when methodological factors and other stressor characteristics were controlled for. Tasks containing both uncontrollable and social-evaluative elements were associated with the largest cortisol and adrenocorticotropin hormone changes and the longest times to recovery. These findings are consistent with the animal literature on the physiological effects of uncontrollable social threat and contradict the belief that cortisol is responsive to all types of stressors.

Stress and the brain: from adaptation to disease

Abstract: In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.

The Concepts of Stress and Stress System Disorders: Overview of Physical and Behavioral Homeostasis

Abstract: Objective. —This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided. Data Sources. —Published original articles from human and animal studies and selected reviews. Literature was surveyed utilizing MEDLINE and the Index Medicus . Study Selection. —Original articles from the basic science and human literature consisted entirely of controlled studies based on verified methodologies and, with the exception of the most recent studies, replicated by more than one laboratory. Many of the basic science and clinical studies had been conducted in our own laboratories and clinical research units. Reviews cited were written by acknowledged leaders in the fields of neurobiology, endocrinology, and behavior. Data Extraction. —Independent extraction and cross-referencing by the authors. Data Synthesis. —Stress and related concepts can be traced as far back as written science and medicine. The stress system coordinates the generalized stress response, which takes place when a stressor of any kind exceeds a threshold. The main components of the stress system are the corticotropin-releasing hormone and locus ceruleus-norepinephrine/autonomic systems and their peripheral effectors, the pituitary-adrenal axis, and the limbs of the autonomic system. Activation of the stress system leads to behavioral and peripheral changes that improve the ability of the organism to adjust homeostasis and increase its chances for survival. There has been an exponential increase in knowledge regarding the interactions among the components of the stress system and between the stress system and other brain elements involved in the regulation of emotion, cognitive function, and behavior, as well as with the axes responsible for reproduction, growth, and immunity. This new knowledge has allowed association of stress system dysfunction, characterized by sustained hyperactivity and/or hypoactivity, to various pathophysiologic states that cut across the traditional boundaries of medical disciplines. These include a range of psychiatric, endocrine, and inflammatory disorders and/or susceptibility to such disorders. Conclusions. —We hope that knowledge from apparently disparate fields of science and medicine integrated into a working theoretical framework will allow generation and testing of new hypotheses on the pathophysiology and diagnosis of, and therapy for, a variety of human illnesses reflecting systematic alterations in the principal effectors of the generalized stress response. We predict that pharmacologic agents capable of altering the central apparatus that governs the stress response will be useful in the treatment of many of these illnesses. ( JAMA . 1992;267:1244-1252)

Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour

Abstract: Recent years have witnessed the rise of the gut microbiota as a major topic of research interest in biology. Studies are revealing how variations and changes in the composition of the gut microbiota influence normal physiology and contribute to diseases ranging from inflammation to obesity. Accumulating data now indicate that the gut microbiota also communicates with the CNS — possibly through neural, endocrine and immune pathways — and thereby influences brain function and behaviour. Studies in germ-free animals and in animals exposed to pathogenic bacterial infections, probiotic bacteria or antibiotic drugs suggest a role for the gut microbiota in the regulation of anxiety, mood, cognition and pain. Thus, the emerging concept of a microbiota-gut-brain axis suggests that modulation of the gut microbiota may be a tractable strategy for developing novel therapeutics for complex CNS disorders.