Receptors autonomic nervous system

Lithium Mechanism of action uncertain suppresses inositol signaling and inhibits glycogen synthase kinase-3 (GSK-3), a multifunctional protein kinase No significant antagonistic actions on autonomic nervous system receptors or specific CNS receptors no sedative effects Bipolar affective disorder-prophylactic use can prevent mood swings between mania and depression Oral absorption, renal elimination half-life 20 h. narrow therapeutic window (monitor blood levels) Toxicity Tremor, edema, hypothyroidism, renal dysfunction, dysrhythmias pregnancy category D Interactions Clearance decreased by thiazides and some NSAIDs... 

Orthostasis Blunting of p response (no tachycardia) Changes in vascular tree Changes in autonomic nervous system Receptor down regulation Blood pressure medications Tricyclic antidepressants Antipsychotics Diuretics... 

It is well established that the autonomic nervous system shows marked plasticity. The expression of cotransmitters and receptors shows dramatic changes during development and ageing, in nerves that remain... 

Smooth muscle cell activity is in general under neural control. Thus, the many transmitters of the autonomic nervous system are paired with receptors on the smooth muscle cell membrane. One of the current questions about smooth muscle function is What intracellular processes are the different transmitters modulating in the smooth muscle cells, in addition to their effects on the contractile state ... 

Dopamine is a catecholamine neurotransmitter in the CNS and at some ganglia in the autonomic nervous system. To date, three main types of receptors have been found D1( D2, and D3. The main dopaminergic systems in the brain are the nigro-neostriatal... 

For each neurotransmitter in the autonomic nervous system, list the neurons that release it and the type and location of receptors that bind with it... 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

Muscarinic receptors are responsible for postganglionic parasympathetic neurotransmission and thus for control of a wide range of smooth muscle, cardiac muscle and secretory responses. Some responses originating in the sympathetic division of the autonomic nervous system, such as sweating and piloerection, also are mediated through muscarinic receptors. 

The effects of both oxytocin and vasopressin are particularly responsive to reproductive steroids (Tables 7 and 8). Oxytocin and vasopressin are best known as neurohypophyseal peptides, released by the posterior pituitary. However, both peptides also are released within the nervous system. Receptors for oxytocin and vasopressin are distributed in areas of the CNS that have been implicated in reproduction, emotion and autonomic functions. 

The autonomic nervous system is itself divided into two parts the sympathetic and parasympathetic nervous systems. The sympathetic nervous system serves several glands and involuntary muscles. The primary neurotransmitter of the sympathetic nervous system is norepinephrine, which acts through a and p adrenergic receptors. 

The concept of chemical transmission in the nervous system arose in the early years of the century when it was discovered that the functioning of the autonomic nervous system was largely dependent on the secretion of acetylcholine and noradrenaline from the parasympathetic and sympathetic nerves respectively. The physiologist Sherrington proposed that nerve cells communicated with one another, and with any other type of adjacent cell, by liberating the neurotransmitter into the space, or synapse, in the immediate vicinity of the nerve ending. He believed that transmission across the synaptic cleft was unidirectional and, unlike conduction down the nerve fibre, was delayed by some milliseconds because of the time it took the transmitter to diffuse across the synapse and activate a specific neurotransmitter receptor on the cell membrane. 

The physiological effects of the catecholamines are mediated by a large number of different receptors that are of particular interest in pharmacology. Norepinephrine acts in the autonomic nervous system and certain areas of the brain. Epinephrine is also used as a transmitter by some neurons. 

Acetylcholine is the primary neurotransmitter in the parasympathetic division of the autonomic nervous system, which mainly innervates the gastrointestinal tract, eyes, heart, respiratory tract, and secretory glands. Although its receptors are crucial for maintaining all normal functions of the body, an extremely small number of illnesses can be explained by the dysfunction of cholinergic regions of the peripheral autonomic system. 

AMS acute myocardial syndrome ANC absolute neutrophil count ANS autonomic nervous system APACHE Acute Physiologic and Chronic Health Evaluation ICU illness severity scoring system APAP acetaminophen [N-acetyl-p-aminof enol] aPTT activated partial thromboplastin time ARB angiotensin 11 receptor blocker ARDS adult respiratory distress syndrome... 

In the sympathetic part of the peripheral autonomic nervous system the simation is less complicated since only the sympathetically innervated visceral organs have receptors sensitive to the transmitter of the postganglionic sympathetic neuron noradrenaline. However, the noradrenaline sensitive receptors, which all belong to the G-protein coupled receptor superfamily, can be subdivided in at least three subtypes ai-, a - and jSi-adrenoceptors. These receptors are to a similar extent sensitive to adrenaline, a humoral transmitter which is released under sympathetic control from the adrenal medulla. Adrenaline, in contrast to noradrenaline has affinity to a forth type, the /32-adrenoceptor. In general drug interacting with the autonomous nervous system can be subdivided according to their mechanism of action. 

Atropine, an alkaloid from Atropa belladonna, is the classical parasympatholytic compound. It competes with acetylcholine for the binding at the muscarinic receptor. Its affinity towards nicotinic receptors is very low, so that it does not interfere with the ganglionic transmission or the neuromotor transmission, at least in therapeutic dosages. However, in the central nervous system muscarinic receptor do play an important role and while atropine can penetrate the blood-brain barrier it exerts pronounced central effects. Atropine, like all other antagonists of the muscarinic acetylcholine receptor inhibit the stimulatory influence of the parasympathetic branch of the autonomous nervous system. All excretory glands (tear, sweat, salivary, gasto-intestinal, bronchi) are... 

Beside this there are some major differences with the neurotransmission in the autonomous nervous system The contractile activity of the skeletal muscle is almost completely dependent on the innervation. There is no basal tone and a loss of the innervation is identical to a total loss in function of the particular skeletal muscle. In contrast to the target organs of the parasympathetic nervous system the skeletal muscle cells only have acetylcholine receptors at the site of the so-called end-plate, the connection between neuron and muscle cell with the rest of the cell surface being insensitive to the transmitter. The release of acetylcholine results in a postjunctional depolarization which is either above the threshold to induce an action potential and a contraction or below the threshold with no contractile response at all. In contrast to the graduated reactions of the parasympathetic target organs, this is an all or nothing transmission. 

Erection involves a coordinated action of the autonomic nervous system, and certain drugs may interfere with either the sympathetic division (e.g., aj- receptors) or the parasympathetic division (e.g., noncholinergic neurotransmitters). 

At present five different muscarinic receptor subtypes are known that mediate the parasympathetic activity of the autonomic nervous system M-,-, M2-, M3-, M4-, and Ms-receptors [88, 116]. The odd-numbered muscarinic receptors are... 

The answer is d. (Hardman, pp 192-193.) Nicotine is a depolarizing ganglionic blocking agent that initially stimulates and then blocks nicotinic muscular (NM) (skeletal muscle) and nicotinic neural (NN) (parasympathetic ganglia) cholinergic receptors. Blockade of the sympathetic division of the autonomic nervous system (ANS) results in arteriolar vasodilation, bradycardia, and hypotension. Blockade at the neuromuscu-... 

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