Receptor, initial stimulation

Initial attempts to treat AD using direct cholinergic agonists were limited by low efficacy and side-effect issues (140—142). Thus trials using RS-86 (25), oxotremorine [70-22-4] (26), arecoline [63-75-2] (27), and pilocarpine [92-32-7] (28) to treat AD were equivocal (Eig. 5). However, the identification of multiple subtypes of muscarinic receptors has stimulated a search for subtype specific muscarinic agonists which may limit side effects while increasing efficacy. 

Null method, physiological or pharmacological effects are translations of biochemical events by the cell. The null method assumes that equal responses emanate from equal initial stimulation of the receptor therefore, when comparing equal responses, the complex translation is cancelled and statements about the receptor activity of agonists can be made. Relative potencies of agonists producing equal responses thus are interpreted to be measures of the relative receptor stimuli produced by the agonists at the receptor see Chapter 5.6.2. 

Stimulus, this is quanta of initial stimulation given to the receptor by the agonist. There are no units to stimulus and it is always utilized as a ratio quantity comparing two or more agonists. Stimulus is not an observable response but is processed by the cell to yield a measurable response. 

There is little doubt that Shallenberger s AH,B hypothesis is the most plausible concept in the explanation of the initial stimulation of the sweet-taste receptor. However, it was unfortunate that the evidence was accrued largely with the aid of reducing sugars, which, in solution, equilibrate between many isomers, so that it is not possible to relate total gustatory response to any one particular stereochemical structure It is also not... 

Low-pressure receptors. The low-pressure receptors are located in the walls of the atria and the pulmonary arteries. Similar to baroreceptors, low-pressure receptors are also stretch receptors however, stimulation of these receptors is caused by changes in blood volume in these low-pressure areas. An overall increase in blood volume results in an increase in venous return an increase in the blood volume in the atria and the pulmonary arteries and stimulation of the low-pressure receptors. These receptors then elicit reflexes by way of the vasomotor center that parallel those of baroreceptors. Because an increase in blood volume will initially increase MAP, sympathetic discharge decreases and parasympathetic discharge increases so that MAP decreases toward its normal value. The simultaneous activity of baroreceptors and low-pressure receptors makes the total reflex system more effective in the control of MAP. 

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-... 

Succinylcholine Agonist at nicotinic acetylcholine (ACh) receptors, especially at neuromuscular junctions depolarizes may stimulate ganglionic nicotinic ACh and cardiac muscarinic ACh receptors Initial depolarization causes transient contractions, followed by prolonged flaccid paralysis depolarization is then followed by repolarization that is also accompanied by paralysis Placement of tracheal tube at start of anesthetic procedure t rarely, control of muscle contractions in status epilepticus Rapid metabolism by plasma cholinesterase normal duration, 5 min Toxicities Arrhythmias hyperkalemia transient increased intraabdominal, intraocular pressure postoperative muscle pain... 

Alpha antagonists are administered primarily to reduce peripheral vascular tone by blocking the alpha-1 receptors located on vascular smooth muscle. When stimulated by endogenous catecholamines (norepinephrine, epinephrine), the alpha-1 receptor initiates vasoconstriction. 

Skeletal muscle twitching is due to effects at the skeletal neuromuscular junction, which is innervated by the somatic nervous system, via motor nerves. The anticholinesterase prolongs and intensifies the actions of released acetylcholine at the junction, causing fasciculation (strong, jerky contractions) of skeletal muscle. Normally at the skeletal neuromuscular junction, the released acetylcholine is rapidly hydrolysed by cholinesterases to choline and acetate. This allows repolarization of the muscle membrane to occur following initial stimulation. In the presence of anticholinesterases the acetylcholine remains at the junction for a very prolonged period and produces repeated twitching of the muscle fibres via nicotinic receptors. 

These drugs act on postsynaptic acetylcholine receptors (cholinoceptors) at all the sites in the body where acetylcholine is the effective neurotransmitter. They initially stimulate and usually later block transmission. In addition, like acetylcholine, they act on the noninnervated receptors that relax vascular smooth muscle in peripheral blood vessels. 

---