Cholinergic, definition

Cholinergic drags have limited usefulness in medicine, pardy because of the adverse reactions that may occur during administration. However, in some diseases or conditions cholinergic drugs are eitiier definitely indicated or may be of value... 

In the mouse, whereas no evidence of H3 receptors was found in isolated gastric glands (Muller et al., 1993), in the whole stomach, (R)a-methylhistamine actually increased, and thioperamide decreased acid secretion, thus indicating a definite stimulatory role for H3 receptors in this species (Table 2). Apparently, this excitatory effect, which contrasts with the observations obtained in other models, was due to an inhibitory effect on somatostatin release from fundic D cells (Schubert et al., 1993 Vuyyuru and Schubert 1993). Also, an inhibitory effect on somatostatin secretion mediated by H3 agonists was observed in other species (rat and dog). However, contrarily to what might have been expected, in these species, the inhibitory effect on somatostatin is not followed by an increase in acid secretion, but it is instead followed by a decrease, owing to the predominant H3-mediated inhibition on the release of excitatory mediators (histamine, acetylcholine) from other sites (ECL, cholinergic nerve terminals)... 

IMS in OP-poisoned patients appears 24-96 h after an apparently well-treated acute cholinergic crisis phase. By definition, OP-poisoned patients should completely recover from the cholinergic crisis and then develop a syndrome. Clinically, IMS is characterized by acute paralysis and weakness in the territories of several cranial motor nerves, neck flexors, facial, extraocular, palatal, nuchal, proximal limb, and respiratory muscles 24-96 h after poisoning. Generalized weakness, depressed deep tendon reflexes, ptosis (drooping of the upper eyelids due to paralysis of the third cranial nerve), and diplopia (double vision of an object) are also evident. These symptoms may last for several days or weeks depending on the OP involved. Despite severe AChE inhibition, muscle fasciculations and muscarinic receptor-associated hypersecretory activities are absent. 

These effects are more likely with antipsychotics, which have no intrinsic antichohneigic action (e.g. butyrophenones), and are less likely with antipsychotics with intrinsic anticholinergic properties (e g. phenothiazines). This is because of the reciprocal actions of DA and cholinergic systems in the basal ganglia. These side-effects, by definition, are also less likely with atypical antipsychotics. 

These low-level exposure definitions refer to the effects observed in a single exposure of less than a 24-h duration. " While a level of AChE inhibition is not mentioned for Level 3 exposures, the symptoms described can be considered cholinergic in nature, probably resulting from inhibition of synaptic AChE. This suggests that a prophylactic approach based on the reduction of the concentration of OP toxicant in the blood before it can reach its site of action (synaptic endplates) should be particularly effective potentially incapacitating or even toxic exposures could be mitigated to Level 3-type outcomes, and lower level exposures could be rendered inconsequential. 

When an action potential traveling down the axon of a motoneuron reaches the myoneural endplate, a process occurs that releases acetylcholine into the synaptic cleft and consequently depolarizes the postsynaptic membrane. A similar process probably occurs at cholinergic synapses in the central nervous system. In 1950 Fatt and Katz discovered a spontaneous subthreshold activity (MEPP) of motor nerve endings and were thereby led to the concept that acetylcholine is released in definite units (quanta) of 10 to 10 molecules. Electron microscopy subsequently revealed characteristic vesicles about 40 nm in diameter, clustered near presynaptic membranes. Subcellular fractionation procedures were devised by Whittaker and de Robertis for the isolation of these vesicles from brain homogenates in sucrose density gradients, and it was soon demonstrated that they were indeed concentrated reservoirs of acetylcholine. The hypothesis that the vesicles discharge the quanta of transmitter became irresistible. 

Campbell, J. B., Woolley, D. E., Vijayan, V. K. and Overmann, S. R. (1982). Morphometric effects of postnatal lead exposure on hippocampal development of the 15-day-old rat. Dev. Brain Res., 3, 595 Carmichael, N. G., Winder, C. and Lewis, P. D. (1981). Dose response relationships during perinatal lead administration in the rat a model for the study of lead effects on brain development. Toxicology, 21, 117 Carmichael, N. G., Winder, C. and Lewis, P. D. (1982). Effects of chronic low level intake on the developing rat brain definition of an experimental system with preliminary findings. Neuropathol. Appl. NeurobioL, 8, 240 Carpenter, S. J. (1974). Placental transfer of lead. Env. Health Perspectives, 7,129 Carroll, P. T., Silbergeld, E. K. and Goldberg, A. M. (1977). Alteration of central cholinergic function by chronic lead acetate exposure. Biochem. Pharmacol, 26, 397... 

A more definite way to solve the issue was the use of affinity labeling for the cholinergic receptor. This method is based on the use of N-maleimido benzyl (or phenyl) trimethylammonium (i.e. MBTA or MPTA) which binds to the anionic site of the receptor and makes a covalent link with a reduced S-S group in its vicinity (Karlin and Cowburn, 1973). With this method and SDS gel electrophoresis... 

A cholinergic innervation has been definitely shown in Mdllusca and Ecfdno-dermata but our knowled is not suflfcient now to determine the localization of all cholinergic neurons. ... 

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