Peptide-catecholamine

The heart, as an endocrine organ itself, secretes the atrial natriuretic peptide, which has several important influences on the cardiovascular system. In addition to atrial natriuretic peptide, catecholamines, thyroid hormones, mineralocorticoids, sex steroids, and angiotensin II are other hormones also known to exert their effects on the cardiovascular functions and blood pressure. Hormones regulate the contraction and dilatation of the vascular bed. They may also affect the contraction of other smooth muscles other than the vascular smooth muscle. Oxytocin stimulates contraction of the myoepithelium in the mammary gland that is necessary for milk ejection. 

Verlander, M. et al. Some novel approaches to the design and thesis of peptide-catecholamine conjugates in Polymers in Medicine Biomedical and Pharmacological Applications (eds.) Chiellini, E., Guisti, P., Plenum Press, 1983 in press... 

APPLICATION OF THE CONGENER APPROACH TO THE DESIGN AND SYNTHESIS OF PEPTIDE-CATECHOLAMINE CONJUGATES... 

Scheme 4 General Synthetic Route to Peptide Catecholamine Conjugates...

M. Goodman, Some novel approaches to the design and synthesis of peptide-catecholamine conjugates. Biopolymers (1983), in press. 

Endothelial cells are the major source of ET-1-synthesis. ET-1 is also produced by astrocytes, neurons, hepatocytes, bronchial epithelial cells, renal epithelial and mesangial cells. Physiological stimuli of ET-1-synthesis in endothelial cells are angiotensin II, catecholamines, thrombin, growth factors, insulin, hypoxia and shear stress. Inhibitors of ET-1 synthesis are atrial natriuretic peptide, prostaglandin E2 and prostacyclin. ET-2 is mainly synthesized in kidney, intestine, myocardium and placenta and ET-3 is predominantely produced by neurons, astrocytes and renal epithelial cells. 

Hi-receptors in the adrenal medulla stimulates the release of the two catecholamines noradrenaline and adrenaline as well as enkephalins. In the heart, histamine produces negative inotropic effects via Hr receptor stimulation, but these are normally masked by the positive effects of H2-receptor stimulation on heart rate and force of contraction. Histamine Hi-receptors are widely distributed in human brain and highest densities are found in neocortex, hippocampus, nucleus accumbens, thalamus and posterior hypothalamus where they predominantly excite neuronal activity. Histamine Hrreceptor stimulation can also activate peripheral sensory nerve endings leading to itching and a surrounding vasodilatation ( flare ) due to an axonal reflex and the consequent release of peptide neurotransmitters from collateral nerve endings. 

Pituitary Adenylyl Cyclase-activating Polypeptide (PACAP) is a 38-amino acid peptide (PACAP-38), which is widely expressed in the central nervous system. PACAP is most abundant in the hypothalamus. It is also found in the gastrointestinal tract, the adrenal gland and in testis. Its central nervous system functions are ill-defined. In the periphery, PACAP has been shown to stimulate catecholamine secretion from the adrenal medulla and to regulate secretion from the pancreas. Three G-protein coupled receptors have been shown to respond to PACAP, PAQ (PACAP type I) specifically binds PACAP, VPACi and VPAC2 also bind vasoactive intestinal peptide (VDP). Activation of PACAP receptors results in a Gs-mediated activation of adenylyl cyclase. 

Simple etching of the capillary end served to decouple the electrophoretic current from that of amperometric detection, permitting quantitation of attomole levels of catecholamines from brain microdialyzates.24 A postcolumn reactor using bromine generated electrochemically in situ has been used in the detection of peptide thiols, such as glutathione and cysteine, separated by capillary electrophoresis.25... 

Inhibition of monoamine oxidase has been proposed as a possible mechanism underlying the hydrogen sulfide-mediated disruption of neurotransmission in brain stem nuclei controlling respiration (Warenycia et al. 1989a). Administration of sodium hydrosulfide, an alkali salt of hydrogen sulfide, has been shown to increase brain catecholamine and serotonin levels in rats. It has also been suggested that persulfide formation resulting from sulfide interaction with tissue cystine and cystinyl peptides may underlie some... 

Feature Steroid hormones Protein/peptide hormones Amine hormones Thyroid hormones Catecholamines ... 

The catecholamines are biologically similar to protein/peptide hormones. These hormones are soluble in the blood and are transported in an unbound form. Therefore, the catecholamines have a relatively short half-life. Because these hormones do not cross cell membranes, they bind to receptors on the membrane surface. Finally, the catecholamines are stored intracellu-larly in secretory granules for future use. 

The most common second messenger activated by protein/peptide hormones and catecholamines is cyclic adenosine monophosphate (cAMP). The pathway by which cAMP is formed and alters cellular function is illustrated in Figure 10.1. The process begins when the hormone binds to its receptor. These receptors are quite large and span the plasma membrane. On the cytoplasmic surface of the membrane, the receptor is associated with a G protein that serves as the transducer molecule. In other words, the G protein acts as an intermediary between the receptor and the second messengers that will alter cellular activity. These proteins are referred to as G proteins because they bind with guanosine nucleotides. In an unstimulated cell, the inactive G protein binds guanosine diphosphate (GDP). When the hormone... 

Figure 10.1 ThecyclicAMPsecondmessengersystem.Themostcommonsecond messenger system activated by the protein/peptide hormones and the catecholamines involves the formation of cAMP. This multistep process is initiated by binding of the hormone (the first messenger) to its receptor on the cell surface. The subsequent increase in the formation of cAMP (the second messenger) leads to the alteration of enzyme activity within the cell. A change in the activity of these enzymes alters cellular metabolism.

The function of peptides as first messengers is evolu-tionarily very old. In phylogenetic terms, neuropeptides were established very early as molecules effecting intercellular communication. In coelenterates, such as Hydra, there are many peptides used in neurotransmission, but many of the conventional neurotransmitter systems, such as acetylcholine (ACh), catecholamines and serotonin,... 

Three of the classes of compounds found from the skin of amphibians have been identified from the skin of bufonids, including Bufo marinus. These are steroids (bufadienolides), biogenic amines (catecholamines, indolylalkylamines and alkaloids) and bioactive peptides and proteins. 

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