Chemical messengers

Describes the different types of chemical messengers in mammalian body. This explains their synthesis and mode of action also. A short account of neurohormones and neuroendocrine function is also included.

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Chemical messengers DR. Radhakrishna G Pillai Department of Life Sciences University of Calicut

Categories of chemical messengers • Local chemical messengers • Neurotransmitters • Neuropeptides • Hormones • Pheromones

Local messengers • Chemical messengers secreted by certain cells • Alter physiological conditions in the immediate vicinity • Act on same cells (Autocrine) or • Adjacent cells (Paracrine) • Do not accumulate in blood • Eg Lumones: produced in gut-regulate digestion – Histamine : secreted by mast cells in wounds- inflammatory response

Autocrine & paracrine controls

Hormones • Signaling molecules synthesized within the body that – regulate and coordinate physiological and metabolic functions • Act on receptors located on or in target cells • Produced by specialized secretory cells that are either – localized in secretary glands or – within organs that have other primary functions • Depending on the cellular origin and the means by which they reach their targets, the cellular messengers are given different names

Hormones • The original definition of hormones was – restricted to chemical messengers – produced within glands of internal secretion and – released into circulation in small quantities to act on distant receptors • The term hormone is derived from the Greek word hormein: to excite

Hormones • Recent definition of hormones also include; – chemical messengers produced by other than specialized secretary cells and – Signaling molecules that reach their target receptors by routes other than circulation – act on the receptors of the cell that produced them – Such messenger action is called autocrine (Greek :autos meaning self)

Paracrine controls • Chemical messengers acting on the receptors of adjacent cells are called paracrine secretions (Greek: word: para, adjacent) – Eg. somatostatin in the pancreatic islets acting on adjacent insulin and glucagon cells

Chemical messengers and their sources

Non glandular sources of CMs

Chemical messenger: mode of actions

Chemical messenger: mode of actions • Chemical messages are transmitted to specific receptors through – the extracellular fluids – across the synaptic gap – blood • When the chemical messengers stimulate receptors on the cell that synthesized them hormone action is autocrine • Messages delivered to adjacent cells: paracrine and • Circulated through plasma: endocrine

Neurotransmission & neuroendocrine action • Nerve cell deliver chemical messages: – in a paracrine fashion across a synaptic gap represent neurotransmission, and – through the blood, neuroendocrine action

Neuro endocrine system • Endocrine system shares its signaling and coordinating function with the nervous system • The two systems have evolved to control and integrate vital body functions • Chemical messengers produced by nerve cells and released from the axonal endings usually act in endocrine or paracrine fashion • Neural signaling molecules released into the synaptic gap to activate receptors on the adjacent cell membranes are called neurotransmitters

Specificity of neurotransmitters • The specificity of the message is assured both by – The specificity of receptors on the postsynaptic membrane & – The discrete physical alignment between axon terminals of a specific type of neuron and the receptors on the postsynaptic membranse of a particular cell

Neurotransmitters Vs hormones • Neurotransmission is characterized by speed of message transmission (milliseconds) and restricted points of delivery • Hormones act over a longer period of time (seconds to hours) and are distributed diffusely through the extracellular fluid/blood medium to a large number of targets

Examples of neurotransmission > Neurotransmitter acetylcholine released from the axonal endings of the motor nerves into the synaptic gap; Act on the nicotinic cholinergic receptors on skeletal and cardiac muscle fibers

Neurohormones • Neural signalling molecules released into circulation are called neuroendocrine secretions or neurohormones • These messengers behave as hormones by their method of signal transmission • They reach their targets through the circulation • The specificity of receptors on target cells assure the delivery of endocrine message to specific targets – Examples: antidiuretic hormone and oxytocin synthesized by the nerve cells residing in hypothalamus and – released into circulation from their nerve endings in the posterior pituitary gland

Neurotransmission or neurosecretion • Some cells disseminate chemical messages by a combination of endocrine and neural mode of communication – Eg. the sympathetic nerves communicate largely by neurotransmission of norepinephrine (NE) – Some NE is released in to general circulation: act as a neuroendocrine messenger • Cells of adrenal medulla are developmentally and evolutionarily ganglionic neurons of the sympathetic nerves: lost their axons • They release epinephrine (E) and NE into systemic circulation • Their function altered from neurotransmission to neurosecretion

Hormones • Eicosanoids: prostaglandins, thromboxanes, leukotrienes, and prostacyclins are group of signaling molecules included as hormones • They are short-lived chemical messengers • They exert autocrine, paracrine, and occasionally endocrine action on their receptors • NO: only inorganic signaling chemical messenger : control a number of important functions

Hormone structure and synthesis • By chemical structure, hormones fall into three groups: amines, peptides and proteins and lipid derivatives • Amine hormones are metabolites of amino acids – Example: epinephrine, norepinephrine and dopamine • They are collectively called catecholamines • Synthesized from the aromatic amino acids phenylalanine and tyrosine in the brain and in the adrenal medulla • Frequently hormones synthesis is under the control of other hormones • Eg. cortisol controls the last enzyme Phenylethanolamine N- methyltransferase (PNMT ) in the synthesis of epinephrine

Hormone production • Epinephrine is synthesized from the aromatic amino acids tyrosine and phenylalanine • Phenylalanine is an essential amino acid that has to be obtained in the diet • Sympathetic nerves and central nervous system synthesize NE • Adrenal medullary cells produce NE and E • Conversion of NE to E in the medulla is facilitated by the adrenal cortical hormone cortisol

Synthesis of catecholamines

Storage and release of hormones

Storage and release of hormones • Hormones are released mainly in two ways • Amine and peptide hormones are stored in storage vesicles before release • Their secretion is controlled by neurotransmitters, hormones or metabolites • Neural influence impose rhythmicity to hormone secretion • Various secretagogues promote fusion of vesicles and cell membrane • The wall of the vesicles rupture • The hormones are given out by exocytosis into blood or extracellular fluid

Storage and release of hormones • Steroid hormones leave the Golgi apparatus in transport vessicles • Released into circulation by exocytosis without being stored within the cytoplasm • This type of hormone secretion is called constitutive • Here the control of hormonal response is at the stage of hormone synthesis rather than hormone release

Regulated release of hormones • Peptide and amine messengers are stored in secretary vesicles • Their release requires transduction of hormonal, neural, and metabolic stimuli by way of intracellular calcium or second messengers • The release of steroid hormones is constitutive • Here hormonal, neural, and metabolic stimuli control steroid hormone synthesis • Immediately the hormone are released from transport vesicles

Quantity released • Hormones are released in nm to picomolar concentrations • They circulate in the blood at such low concentrations • Success of hormone mediated response transmission rely on the specificity and high affinity of their binding to the receptors • Most hormones are secreted in intermittent rather than continuous fashion • Pulsatile hormone secretion probably serves to supply hormones in quantities required for their action

Frequency of hormone release • The frequency of basal hormone pulses ranges from minutes to hours • There are also seasonal rhythms of hormone release • Various stimuli can acutely increase or decrease hormone secretion • Eg. acute change in secretion of some hormones during exercise • Compensatory changes in hormone secretion usually result from metabolic, neural or hormonal feedback • This feedback control is over the normal hormone secretion signaling: the secretion rate is out of alignment with the acute need for hormone action

Pattern of hormone release and its effect • The temporal pattern of hormone secretion is of remarkable biological significance • The same quantity of hormone can have opposite biological functions when it is delivered in intermittent as opposed to tonic fashion • Eg. lack of growth stimulation by tonic administration of GH • Normal menstrual function by a circhoral (1 pulse/hr) secretion of LH • Lower or higher or tonic release of LH suppress menstrual cycle • Modulation of biological response by changes in the temporal pattern of hormone secretion is often exploited for specific purposes • Tonic administration of gonadotropins has been successfully used to achieve contraception

Transport of hormones • Peptide, amine and protein hormones are water soluble, and most of them circulate freely • All of lipophilic steroid hormones, growth hormone and some growth factors circulate bound to carrier proteins • Albumin and pre albumin non-selectively bind to and transport a variety of small messenger molecules • Globulins have single high-affinity binding sites for specific steroid and amine hormones

Importance of hormone binding to carriers • Binding hormones to carriers extends the period of their availability and action by – Preventing their rapid clearance from plasma – By keeping some of the hormone from circulating in the free form and diminish the magnitude but extend the duration of hormone action – Insulin-like growth factors are protected from degradation and the duration of their biological action extended for hours by the complex system of binding proteins • In some instances (for example GH), binding proteins have almost identical structure to cell receptors and may facilitate the binding of the hormone to the receptor • Thus the binding proteins may facilitate hormone action

Degradation of Hormone • To be most effective, hormones need to reach their target receptors in intermittent fashion. Why? • Receptors become down regulated or less sensitive to hormone action when; – hormones are present in unphysiologically high concentrations or – for abnormally long periods of times • Hormone degradation avoids these situations • Hence it is necessary prerequisite for optimal hormone sensitivity and action

Degradation of hormones • Hormones are changed into metabolicaly inactive form either in target cells or in the liver and kidney • A number of enzymes participate in metabolic degradation of hormones • The speed with which the hormones are metabolized depends on; – whether they travel free in plasma – as well as on their molecular structure and – the characteristics and location of their degrading enzymes • The half-lives of hormones vary from seconds to hours

Half life of some chemical messengers

Thank you pillai_radhakrishna@hotmail.com 0091 9495554891

Editor’s Notes