Physiology of cholinergic and adrenergic synapses. Role in pharmacology and practical significance

The transmission of signals between cholinergic neurons and from neurons to muscle cells (neuro-neuronal and neuromuscular transduction) occurs through synapses. They are formed by the membranes of two contacting cells, presynaptic and postsynaptic, which are separated by a narrow synaptic gap. The review article provides up-to-date information about the physiological processes in cholinergic and adrenergic synapses. The role of these synapses in pharmacology and their practical significance are presented. The transmission of excitation in cholinergic synapses occurs with the help of acetylcholine. The stages of synthesis, storage and release of acetylcholine are the same in all cholinergic neurons. The specific effects of acetylcholine mediated through cholinergic synapses depend mainly on the type of synaptic cholinergic receptors. In the system of efferent innervation, adrenergic synapses are formed by the endings of postganglionic sympathetic (adrenergic) fibers and cells of effector organs.

The autonomic innervation of hairy skin in humans: an in vivo confocal study

The autonomic innervation of the skin includes different subsets of adrenergic and cholinergic fibers both in humans and animals. The corresponding chemical code is complex and often difficult to ascertain. Accordingly, a detailed histochemical description of skin autonomic fiber subtypes is lacking in humans. To characterize skin autonomic nerve subtypes may help to better understand the selective damage of specific skin autonomic fibers affecting human diseases such as the adrenergic fibers directed to skin vessels in Parkinson’s disease or the cholinergic sudomotor fibers in Ross Syndrome. The present study aimed at characterizing subtypes of autonomic fibers in relation to their target organs by means of an immunofluorescent technique and confocal microscopy. We studied 8 healthy subjects (5 males and 3 females) aged 45 ± 2 (mean ± SE) years without predisposing causes for peripheral neuropathy or autonomic disorders. They underwent skin biopsy from proximal (thigh) and distal (leg) hairy skin. A combination of adrenergic (i.e. tyrosine-hydroxylase- TH and dopamine beta-hydroxylase- DbH) and cholinergic (vesicular acetylcholine transporter- VACHT) autonomic markers and neuropeptidergic (i.e. neuropeptide Y- NPY, calcitonin gene-related peptide- CGRP, substance P- SP, and vasoactive intestinal peptide- VIP) markers were used to characterize skin autonomic fibers. The analysed skin autonomic structures included: 58 sweat glands, 91 skin arterioles and 47 arrector pili muscles. Our results showed that all skin structures presented a sympathetic adrenergic but also cholinergic innervation although in different proportions. Sympathetic adrenergic fibers were particularly abundant around arterioles and arrector pili muscles whereas sympathetic cholinergic fibers were mainly found around sweat glands. Neuropeptides were differently expressed in sympathetic fibers: NPY were found in sympathetic adrenergic fibers around skin arterioles and very seldom sweat glands but not in adrenergic fibers of arrector pili muscles. By contrast CGRP, SP and VIP were expressed in sympathetic cholinergic fibers. Cholinergic fibers expressing CGRP, SP or VIP without TH or DbH staining were found in arterioles and arrector pili muscles and they likely represent parasympathetic fibers. In addition, all skin structures contained a small subset of neuropeptidergic fibers devoid of adrenergic and cholinergic markers with a likely sensory function. No major differences were found between males and females and proximal and distal sites. In summary hairy skin contains sympathetic adrenergic and cholinergic fibers differently distributed around skin structures with a specific distribution of neuropeptides. The autonomic skin innervation also contains a small amount of fibers, likely to be parasympathetic and sensory.

Case 55: Small Fiber Neuropathy with Autonomic Failure

This case demonstrates severe autonomic failure with orthostatic hypotension affecting cardiovagal and sympathetic adrenergic fibers and associated with small fiber neuropathy. Small fiber neuropathy is severe, mixed, and affecting sensory and autonomic fibers, non–length-dependent. Orthostatic cerebral blood flow velocity was reduced throughout the tilt, indicative of autoregulation failure.

The Effect of Dexmedetomidine on Oral Mucosal Blood Flow and the Absorption of Lidocaine

Dexmedetomidine (DEX) is a sedative and analgesic agent that acts via the alpha-2 adrenoreceptor and is associated with reduced anesthetic requirements, as well as attenuated blood pressure and heart rate in response to stressful events. A previous study reported that cat gingival blood flow was controlled via sympathetic alpha-adrenergic fibers involved in vasoconstriction. In the present study, experiment 1 focused on the relationship between the effects of DEX on alpha adrenoreceptors and vasoconstriction in the tissues of the oral cavity and compared the palatal mucosal blood flow (PMBF) in rabbits between general anesthesia with sevoflurane and sedation with DEX. We found that the PMBF was decreased by DEX presumably because of the vasoconstriction of oral mucosal vessels following alpha-2 adrenoreceptor stimulation by DEX. To assess if this vasoconstriction would allow decreased use of locally administered epinephrine during DEX infusion, experiment 2 in the present study monitored the serum lidocaine concentration in rabbits to compare the absorption of lidocaine without epinephrine during general anesthesia with sevoflurane and sedation with DEX. The depression of PMBF by DEX did not affect the absorption of lidocaine. We hypothesize that this is because lidocaine dilates the blood vessels, counteracting the effects of DEX. In conclusion, despite decreased palatal blood flow with DEX infusion, local anesthetics with vasoconstrictors should be used in implant and oral surgery even with administered DEX.