Gastric acid secretion central

Histamine is a biogenic amine that is widely distributed in the body and functions as a major mediator of inflammation and allergic reactions, as a physiological regulator of gastric acid secretion in the stomach, as a neurotransmitter in the central nervous system (CNS) and may also have a role in tissue growth and repair. 

Pharmacology The methyixanthines (theophylline, its soluble salts and derivatives) directly relax the smooth muscle of the bronchi and pulmonary blood vessels, stimulate the CNS, induce diuresis, increase gastric acid secretion, reduce lower esophageal sphincter pressure, and inhibit uterine contractions. Theophylline is also a central respiratory stimulant. Aminophylline has a potent effect on diaphragmatic contractility in healthy people and may then be capable of reducing fatigability and thereby improve contractility in patients with chronic obstructive airways disease. Pharmacokinetics ... 

The principal xanthines of medical interest include caffeine, theophylline and aminophylline. Caffeine is synthesized by several plants and was originally isolated from tea in 1838. It is a methylxanthine (Figure 1.12) which stimulates the central nervous system, increasing mental alertness. It also acts as a diuretic and stimulates gastric acid secretion. It is absorbed upon oral administration and is frequently included in drugs containing an analgesic, such as aspirin or paracetamol. 

In the mucosa of the gastrointestinal tract histamine is present in enterochromaffin cells. These cells are thought to contain the histamine which is involved in the stimulation of gastric acid secretion. In the central nervous system there are histaminergic neurons. 

Barocelli, E., Ballabeni, V., Chiavarini, M., Impicciatore, M., 1995. R-a-methylhistamine-induced inhibition of gastric acid secretion in pylorus-ligated rats via central histamine H3 receptors. Br. J. Pharmacol. 115, 1326-1330. 

Apart from its role as a major mediator of inflammation and allergic reactions and as physiological regulator of gastric acid secretion, histamine is also a neurotransmitter in the CNS. Central histaminergic cell bodies are located in the posterior hypothalamus and project diffusely to almost all brain regions and to the spinal cord. There are four types of histamine receptors, all G-protein-coupled, Hi, H2, H3 and H4. Hi receptors couple to Gq/11 proteins. H2 receptors couple to Gs. H3 and H4 receptors couple to Gi/o. 

Gastric acid secretion may be regulated by several brain peptides, some of which may enhance secretion, while others may act centrally to inhibit secretion. 

The principal actions of these peptides are to stimulate gastric acid secretion, to contract intestinal smooth muscle and to contract or relax a range of vascular tissues. A number of neurons in the enteric and central nervous system are excited. Supposed roles for the peptides include a role as a major excitatory enteric neurotransmitter, in central neuronal processes, particularly in feeding and satiety processes and for GRP include a role in facilitating gastric acid secretion. 

VIP has a large number of ill-defined physiological actions, some of which are shared with other similar polypeptide hormones (secretin and GIF). It acts as a neurotransmitter in the central and autonomic nervous systems and causes vasodilation and relaxation of the smooth muscles of the circulatory and genitourinary systems and the gut. Other actions of VIP include an increase of water and electrolyte secretion from the pancreas and gut release of hormones from the pancreas, gut, and hypothalamus stimulation of lipolysis, glycolysis, and bile flow and inhibition of gastrin and gastric acid secretion. Most of the actions of VIP tend to be of short duration because of its rapid degradation. 

Stimulation of parietal cells for gastric acid secretion is a complex process mediated both centrally by vagal parasympathic fibers and peripherically by release of histamine from the fundic mucosal enterochromaffin-like... 

The primary indication for theophylline is as a controller medication for the treatment of bronchospasm of asthma and COPD. In addition to bronchodilation effects, theophylline dilates pulmonary blood vessels, acts centrally to stimulate respiration, acts as a diuretic, increases gastric acid secretion, and inhibits uterine contractions. Dosing requires the determination of plasma levels with 10 to 20 pg/mL being associated with the least incidence of side effects. Overdose of theophylline can result in a quick onset of ventricular arrhythmias, convulsions, or even death... 

Whereas Hi receptors are involved with positive effects, H2 receptors appear to mainly mediate suppressive activities of histamine including gastric acid secretion, heart contraction, cell proliferation, differentiation, and some effects on the immune response. H2 receptors are coupled to the adenylate cyclase as well as the phosphoinositide second messenger systems via separate GTP-dependent mechanisms, but H2-dependent effects, particularly those of the central nervous system, are predominantly mediated through cAMP. It has been shown that receptor binding stimulates activation of c-Fos, c-Jun, PKC, and P70S6 kinase. Alternative signaling pathways have been reported (Fig. 3.7). These include a receptor-mediated increase in intracellular Ca and/or IP3 levels in HL-60 human promyelocytic leukemia cells and an increase in cAMP and inhibition of release of arachidonic acid in Chinese hamster ovary (CHO) cells transfected with rat cDNA and induced by calcium ionophore. 

CCK is found in the digestive tract and the central and peripheral nervous systems. In the brain, CCK coexists with DA. In the peripheral nervous system, the two principal physiological actions of CCK are stimulation of gaU. bladder contraction and pancreatic enzyme secretion. CCK also stimulates glucose and amino acid transport, protein and DNA synthesis, and pancreatic hormone secretion. In the CNS, CCK induces hypothermia, analgesia, hyperglycemia, stimulation of pituitary hormone release, and a decrease in exploratory behavior. The CCK family of neuropeptides has been impHcated in anxiety and panic disorders, psychoses, satiety, and gastric acid and pancreatic enzyme secretions. 

Like many other neuropeptides, NT serves a dual function as a neurotransmitter or neuromodulator in the central nervous system and as a local hormone in the periphery. When administered centrally, NT exerts potent effects including hypothermia, antinociception, and modulation of dopamine neurotransmission. When administered into the peripheral circulation, it causes vasodilation, hypotension, increased vascular permeability, increased secretion of several anterior pituitary hormones, hyperglycemia, inhibition of gastric acid and pepsin secretion, and inhibition of gastric motility. It also exerts effects on the immune system. 

Treatment of peptic ulceration has traditionally centred around measures to neutralise gastric acid, to inhibit its secretion, or to enhance mucosal defences. More recently, recognition of the central role of Helicobacter pylori has revolutionised treatment. Smoking is a major environmental factor and patients who smoke should be advised to stop. 

---