Vasoactive peptides substance

These are a family of peptides which include substance P, isolated in 1931 but only sequenced in 1971. This peptide has been extensively studied since it was the first major peptide to be extracted from brain but only now are useful antagonists becoming available. Two closely related peptides were then isolated from mammalian tissues and can be added to a number of other tachykinins, many of which are found in amphibians. The name tachykinins originated from the vasoactive effects of substance P but the nomenclature has been resolved into calling the three major mammalian peptides substance P, neurokinin A (NKA) and neurokinin B (NKB) with the corresponding receptors being numbered 1 to 3. The order of potencies at the three receptors as follows ... 

Peptides are used by most tissues for cell-to-cell communication. As noted in Chapters 6 and 21, they play important roles in the autonomic and central nervous systems. Several peptides exert important direct effects on vascular and other smooth muscles. These peptides include vasoconstrictors (angiotensin II, vasopressin, endothelins, neuropeptide Y, and urotensin) and vasodilators (bradykinin and related kinins, natriuretic peptides, vasoactive intestinal peptide, substance P, neurotensin, calcitonin gene-related peptide, and adrenomedullin). This chapter focuses on the smooth muscle actions of the peptides. 

Autacoids Endogenous substances with compiex physioiogic and pathophysioiogic functions commoniy interpreted to inciude histamine, serotonin, prostagiandins, and vasoactive peptides... 

Describe the effects of vasoactive intestinal peptide, substance P. and calcitonin gene-related peptide. 

A. Classification and Prototypes Vasoactive peptides comprise a large class of endogenous substances that function as neurotransmitters as well as local and systemic hormones. The better-known peptides include angiotensin, bradykinin, atrial natriuretic peptide, endothelin, vasoactive intestinal peptide, substance P, calcitonin gene-related peptide, vasopressin, glucagon, and several opioid peptides. Vasopressin is discussed in Chapters 15 and 37, the opioid peptides in Chapter 31, and glucagon in Chapter 41. The peptides discussed in this chapter and their effects are summarized in Table 17-1. 

VASOACTIVE INTESTINAL PEPTIDE, SUBSTANCE P, CALCITONIN GENE-RELATED PEPTIDE, NEUROPEPTIDE Y... 

The release of some peptides may differ from that of other transmitters, depending on the firing rate of the neurons. The large vesicles needed to store a peptide may need a greater rate of depolarisation for membrane fusion and release of the contents. In the salivary gland the release of vasoactive intestinal polypeptide requires high-frequency stimulation whereas acetylcholine is released by all stimuli. Due to the complexities and problems of access to CNS synapses it is not known if the same occurs here but there is no reason why this should not. In sensory C-fibres a prolonged stimulus appears to be a prerequisite for the release of substance P. 

Secretory diarrhea occurs when a stimulating substance (e.g., vasoactive intestinal peptide [VIP], laxatives, or bacterial toxin) increases secretion or decreases absorption of large amounts of water and electrolytes. 

The innervation of the gastrointestinal tract is complex. The myenteric and submucosal plexuses contain many interneurons. These possess a number of neurotransmitters and neuromodulators, including several peptides, such as enkephalins, substance P, and vasoactive intestinal peptide. Reflex activity within the plexuses regulates peristalsis and secretion locally. The effects of sympathetic and parasympathetic nerve stimulation are superimposed on this local neural regulation. 

Stimulation of 5-HT4 receptors on the presynaptic terminal of submucosal intrinsic primary afferent nerves enhances the release of their neurotransmitters, including calcitoningene-related peptide, which stimulate second-order enteric neurons to promote the peristaltic reflex (Figure 62-4). These enteric neurons stimulate proximal bowel contraction (via acetylcholine and substance P) and distal bowel relaxation (via nitric oxide and vasoactive intestinal peptide). 

The heterogeneity of dopaminergic neurons may also be judged by the fact that the cotransmitter systems involving dopamine and peptides are varied in the central nervous system. For example, in the corpus striatum, in addition to dopamine, acetylcholine, y-aminobutyric acid, serotonin, glutamate, and aspartate, one also finds peptides such as enkephalin, substance P, somatostatin, neuropeptide Y, cholecystokinin, neurotensin, and vasoactive intestinal peptide. Although many neuroleptics block dopamine receptors, they may have selective effects on the peptides and other parts of the brain. A few examples will be cited. 

The expression of the ET-1 gene is increased by growth factors and cytokines, including transforming growth factor-B (TGF-B) and interleukin 1 (IL-1), vasoactive substances including angiotensin II and vasopressin, and mechanical stress. Expression is inhibited by nitric oxide, prostacyclin, and atrial natriuretic peptide. 

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