TL;DR: This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration.
Abstract: This review is focused on purinergic neurotransmission, i.e., ATP released from nerves as a transmitter or cotransmitter to act as an extracellular signaling molecule on both pre- and postjunctional membranes at neuroeffector junctions and synapses, as well as acting as a trophic factor during development and regeneration. Emphasis is placed on the physiology and pathophysiology of ATP, but extracellular roles of its breakdown product, adenosine, are also considered because of their intimate interactions. The early history of the involvement of ATP in autonomic and skeletal neuromuscular transmission and in activities in the central nervous system and ganglia is reviewed. Brief background information is given about the identification of receptor subtypes for purines and pyrimidines and about ATP storage, release, and ectoenzymatic breakdown. Evidence that ATP is a cotransmitter in most, if not all, peripheral and central neurons is presented, as well as full accounts of neurotransmission and neuromodulation in autonomic and sensory ganglia and in the brain and spinal cord. There is coverage of neuron-glia interactions and of purinergic neuroeffector transmission to nonmuscular cells. To establish the primitive and widespread nature of purinergic neurotransmission, both the ontogeny and phylogeny of purinergic signaling are considered. Finally, the pathophysiology of purinergic neurotransmission in both peripheral and central nervous systems is reviewed, and speculations are made about future developments.
TL;DR: The rhythm generating mechanisms may help to restrict rates of individual fibres to the low range which provides high gain in the neuroeffector transfer functions.
Abstract: 1. Recordings of multiunit sympathetic activity were made from human nerve fascicles supplying hairy and glabrous skin of the extremities in healthy subjects exposed to different ambient temperatures. Sudomotor and vasomotor events accompanying the neural activity were monitored by simultaneous recordings of electrodermal and pulse plethysmographic events (Pleth) in the neural innervation zones. 2. By exposing the subject to warm (43 degrees C) or cold (15 degrees C) environments, it was possible to obtain a selective activation of either the sudomotor or the vasoconstrictor neural system, respectively, with suppression of spontaneous activity in the other system. 3. Bursts of both vasoconstrictor and sudomotor nerve activity were found to occur at certain preferred intervals which were integer multiples of a period of about 0 . 6 sec (100 cycles/min). With high sudomotor or vasoconstrictor tone the 100 cycles/min rhythm was prominent but with decreasing tone slower subharmonic rhythms prevailed. Respiratory rhythms were also discerned as well as slower rhythms attributable to oscillatory tendencies in thermoregulatory servos. 4. Vasoconstrictor bursts had longer mean duration than sudomotor bursts, a finding attributed to a slower conduction velocity of vasoconstrictor as compared to sudomotor impulses. 5. With increasing incidence of bursts transient electrodermal or plethysmographic responses following individual bursts merged, and thus the fast neural rhythms were not discernible in either the electrodermal or Pleth traces. Given increments in firing rate of nerves produced less additional vasoconstriction at high than at low firing rates. The rhythm generating mechanisms may help to restrict rates of individual fibres to the low range which provides high gain in the neuroeffector transfer functions.
TL;DR: This procedure ensures adequate penetration of the antibody molecules without the need to freeze and thaw the tissue or to use detergents, preserves antigenicity and lowers non-specific background staining.
Abstract: A method is described for the immunohistochemical localization of peptides in whole-mount preparations. Tissue is fixed as laminae with a picric acid/formaldehyde mixture and then dehydrated, cleared and rehydrated before exposure to antibodies. This procedure ensures adequate penetration of the antibody molecules without the need to freeze and thaw the tissue or to use detergents, preserves antigenicity and lowers non-specific background staining. The laminae are incubated with the primary antisera for 16 h at room temperature and, after washing, with a second, fluorescent tagged, antiserum. This can be followed by a peroxidase-anti-peroxidase localization of the second antiserum, which acts as a bridge. The method gives a precise and reproducible localization of immunoreactive peptides, with good penetration and low background even in thick preparations. Large areas can be scanned and neuroeffector relationships studied more easily than in sections.
TL;DR: Data indicate that potentially important differences exist in the regulatory behavior of components of the beta-adrenergic receptor-G protein-adenylate cyclase complex in IDC versus ISCDC, differences that presumably relate to the distinct pathophysiologies of these two types of heart muscle disease.
Abstract: BACKGROUNDWe measured the content and activities of components of the beta-adrenergic receptor-G protein-adenylate cyclase complex and adrenergic neurotransmitter levels in left and right ventricular myocardial preparations derived from 77 end-stage failing human hearts from patients with idiopathic dilated cardiomyopathy (IDC) or ischemic dilated cardiomyopathy (ISCDC).METHODS AND RESULTSThe results were compared with data obtained in 21 nonfailing hearts removed from organ donors. Compared with ISCDC ventricles, IDC left and right ventricles exhibited a greater degree of total beta- or beta 1-receptor downregulation. In contrast, compared with IDC right ventricles, isolated tissue preparations of ISCDC right ventricles exhibited a greater degree of subsensitivity to the inotropic effect of isoproterenol, indicating a relatively greater degree of functional uncoupling of right ventricular ISCDC beta-receptors from mechanical response. In addition, relative to IDC left ventricles, preparations of ISCDC le...