Effector, autonomic

Besides the arterial baroreceptors, central projections from other inputs, for example cardiac mecha-no-receptors, chemo-receptors, pulmonary stretch receptors, and somatic inputs, are capable of influencing the controlling system and thereby the autonomic effectors. 

Muscarine is a natural alkaloid that is found in a number of wild mushrooms. Despite the fact that muscarine does not have any therapeutic value, it is of interest because of its expressed toxic properties, which made it one of the first systematically studied cholinomimetic substances. This compound was an underlying classification of cholinergic muscarinic receptors. The action of muscarine is similar to that of acetylcholine on peripheral autonomic effector organs, and atropine is an antagonist to it. Unlike acetylcholine, muscarine does not act on nicotinic receptors. 

Both somatic and autonomic effectors may be re-flexly excited by nerve impulses arising from the same sensory end organs. For example, when the body is exposed to cold, heat loss is minimized by vasoconstriction of blood vessels in the skin and by the curling up of the body. At the same time, heat production is increased by an increase in skeletal muscle tone and shivering and by an increase in metabolism owing in part to secretion of epinephrine. 

If the poisoning is due to an organophosphate, prompt administration of pralidoxime chloride will result in dephosphorylation of cholinesterases in the periphery and a decrease in the degree of the blockade at the skeletal neuromuscular junction. Since pralidoxime is a quaternary amine, it will not enter the CNS and therefore cannot reactivate central cholinesterases. In addition, pralidoxime is effective only if there has been no aging of the phosphorylated enzyme. Pralidoxime has a greater effect at the skeletal neuromuscular junction than at autonomic effector sites. 

It has been known for many years that autonomic effector tissues (eg, gut, airways, bladder) contain nerve fibers that do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Both motor and sensory NANC fibers are present. Although peptides are the most common transmitter substances found in these nerve endings, other substances, eg, nitric oxide synthase and purines, are also present in many nerve terminals (Table 6-1). Capsaicin, a neurotoxin derived from chili peppers, can cause the release of transmitter (especially substance P) from such neurons and, if given in high doses, destruction of the neuron. 

The sensory fibers in the nonadrenergic, noncholinergic systems are probably better termed "sensory-efferent" or "sensory-local effector" fibers because, when activated by a sensory input, they are capable of releasing transmitter peptides from the sensory ending itself, from local axon branches, and from collaterals that terminate in the autonomic ganglia. These peptides are potent agonists in many autonomic effector tissues. 

The eye is a good example of an organ with multiple autonomic nervous system (ANS) functions, controlled by several autonomic receptors. As shown in Figure 6-9, the anterior chamber is the site of several autonomic effector tissues. These tissues include three muscles (pupillary dilator and constrictor muscles in the iris and the ciliary muscle) and the secretory epithelium of the ciliary body. 

Early studies of the parasympathetic nervous system showed that the alkaloid muscarine mimicked the effects of parasympathetic nerve discharge that is, the effects were parasympathomimetic. Application of muscarine to ganglia and to autonomic effector tissues (smooth muscle, heart, exocrine glands) showed that the parasympathomimetic action... 

Table 6-2. Autonomic Receptor Types with Documented or Probable Effects on Peripheral Autonomic Effector Tissues. ...

Hyoscine competitively inhibits the actions of acetylcholine at the muscarinic receptors of autonomic effector sites innervated by parasympathetic nerves. It has a central as well as a peripheral action, as it is lipid-soluble and crosses the blood-brain barrier. 

Stimulation or inhibition of autonomic effector cells by ACh results from interaction of ACh with muscarinic ACh receptors. In this case, the effector is coupled to the receptor by a G protein (see Chapter 1). In contrast to skeletal muscle and neurons, smooth muscle and the cardiac conduction system (sinoatrial [SA] node, atrium, atrioventricular [AV] node, and the His-Purkinje system) normally exhibit intrinsic activity, both electrical and mechanical, that is modulated but not initiated by nerve impulses. At some smooth muscle, ACh causes a decrease in the resting potential (i.e., the membrane potential becomes less negative) and an increase in the frequency of spike production, accompanied by a rise in tension. A primary action of ACh in initiating these effects through muscarinic receptors is probably partial depolarization of the cell membrane brought about by an increase in Na and, in some instances, Ca conductance activation of muscarinic receptors can also activate the G -PLC-IP pathway leading to the mobilization of stored Ccf. Hence, ACh stimulates ion fluxes across membranes and/or mobilizes intracellular Ca to cause contraction. 

Actions of acetylcholine (ACh) are referred to as muscarinic based on the observation that muscarine acts selectively at certain sites and, quahtatively, produces the same effects as ACh. Peripheral muscarinic acetylcholine receptors are found primarily on autonomic effector cells innervated by postganghonic parasympathetic nerves and on some cells that receive little or no cholinergic innervation but express muscarinic receptors e.g., vascular endothelial cells). There are also muscarinic receptors in ganglia and the adrenal meduUa, where muscarinic stimulation seems to modulate the effects of nicotinic stimulation. Within the central nervous system (CNS), the hippocampus, cortex, and thalamus have high densities of muscarinic receptors. 

PHARMACOLOGY, TOXICOLOGY, AND DISPOSITION The reactivating action of oximes in vivo is most marked at the skeletal neuromuscular junction. Following a dose of an organophosphorus compound that produces total blockade of transmission, the intravenous injection of an oxime restores responsiveness of the motor nerve to stimulation within minutes. Antidotal effects are less striking at autonomic effector sites, and the quaternary ammonium group restricts entry into the CNS. 

Name the major types of receptors found on autonomic effector tissues. 

Autonomic effector cells or tissues Cells or tissues that have adrenoceptors or cholinoceptors which, when activated, alter the function of those cells or tissues, eg, smooth muscle, heart, glands... 

E. Nonadrenergic, Noncholinergic (NANC) Transmission Some nerve fibers in autonomic effector tissues do not show the histochemical characteristics of either cholinergic or adrenergic fibers. Some of these are motor fibers that cause the release of ATP and possibly other purines related to it. Purine-evoked responses have been identified in the bronchi, gastrointestinal tract, and urinary tract. Other motor fibers are peptidergic, ie, they release peptides as the primary transmitters (see list above under Cotransmitters). 

Parasympatholytic A drug that blocks the muscarinic receptors of autonomic effector tissues and reduces the effects of parasympathetic nerve stimulation... 

Which of the following act primarily on a receptor located on the membrane of the autonomic effector cell, ie, muscle or glandular tissue ... 

Acetylcholine is the endogenous neurotransmitter of the parasympathetic nervous system. The parasympathetic nerve fibers are found in both the autonomic and central nervous systems. These fibers are classified into those that are stimulated by muscarine and those that are stimulated by nicotine. Nicotine, an alkaloid Uom Nicotiana tabacum, stimulates preganglionic fibers in both the parasympathetic and sympathetic systems as well as the somatic motor fibers of the skeletal system. Muscarine, an alkaloid from the poisonous mushroom Amanita muscaria, stimulates postganglionic parasympathetic fibers with receptors found on autonomic effector... 

The Folkow school knew that the customary frequency of impulses in autonomic effector nerves is less than 10 sec" , and Martinson used either 4 or 8 sec . He began with an impulse duration of 0.05 msec, and as he increased the duration to 1 msec he saw a linear increase in gastric motor excitation. Secretion and blood flow were never affected by impulses having a duration of 0.1 msec or less, but as impulse duration was increased above 0.1 msec, secretion of acid and pepsin and blood flow increased. Thus, Martinson found two distinct sets of efferent fibers in the vagus having different thresholds for excitation and different functions. In addition, he found high-threshold fibers that mediated relaxation of the stomach, a phenomenon first observed by Cannon and Lieb in 191... 

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