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S Fidone

Publications and source records attributed to S Fidone.

48 records · Page 3Linked to original sources

Physiological and pharmacologic effects on TH activity in rabbit and cat carotid body.

The carotid bodies, along with the superior cervical ganglia and the adrenal glands, were removed from rabbits and cats and the activity of tyrosine hydroxylase (TH), the rate-limiting enzyme in catecholamine biosynthesis, was assayed by the method of Nagatsu (Anal. Biochem. 9: 122-126, 1964). The activities of the enzyme, in nmols tyrosine hydroxylated x h-1 x mg tissue-1, were: carotid body, rabbit 1.29, cat 0.84; superior cervical ganglion, rabbit 8.66, cat 4.97; adrenal gland, rabbit 0.95, cat 2.25. With respect to the carotid body, each of the following experimental procedures resulted in a long-term increase in TH activity in the rabbit but not in the cat: 1) severe hypoxia (5% O2 in N2 for 1 h, assay of TH 48 h later); 2) chronic transection of the carotid sinus nerve (assay of TH at 12-15 days); or 3) administration of reserpine (10 mg/kg at 0 and 24 h, assay of TH at 48 h). These observations are compared with our previous findings for rat carotid body and are discussed in relation to the role of catecholamines in chemoreception, and, in particular, to the reported differences in dopamine action in the carotid bodies of these different species. Our results also suggest species differences with respect to the participation of the sympathoadrenal system in response to reserpine and hypoxic stress.

Adrenal Glands↗

Membrane potentials recorded from the mucosa of the toad's tongue during chemical stimulation.

An isolated stretch of tongue mucosa was obtained from the Chilean toad (Callyptocephalella gayi). The preparation was observed under transmitted illumination through a binocular microscope. The surface cells were impaled with micro-electrodes and different chemical agents were applied to the area. The following results were obtained.1. The surface cells had resting potentials of -6 to -40 mV (mean of -17.6 mV) with the preparation bathed in Ringer solution.2. The cells underwent depolarization by application of different salts (NaCl, NaF, KCl, Na(2)SO(4), CaCl(2) and MgCl(2)) in concentrations of 0.25-1.0 M. The potentials evoked by the salt solutions often overshot the zero membrane potential level by several millivolts. The positive-going potential change produced by application of salts was increased during hyperpolarization of the membrane by inward current and was decreased by current of the opposite sign. Application of salts during depolarization of the membrane to a certain positive level produced a negative-going potential change. The potentials evoked by different salts were about the same, qualitatively, when recordings were made from different areas of the tongue, i.e. top of the fungiform and filiform papillae, doughnut-shaped folds at the base of the fungiform papillae, areas between papillae and from the side of the tongue totally devoid of papillary structures.3. Quinine applied in concentrations of 2 x 10(-2)M did not change the resting polarization of the surface epithelial cells. However, quinine applied to cells already depolarized by outward currents induced further depolarization. When it was delivered to cells hyperpolarized by inward current the substance induced further hyperpolarization.4. Sucrose (0.5-1.0 M) did not change the membrane potential of lingual cells regardless of the level of cell polarization induced by injected currents.5. Hydrochloric, sulphuric, nitric and acetic acids produced minimal biphasic effects: a brief hyperpolarization followed by a slower secondary depolarization.6. Water increased the membrane potential of the surface cells. Salts applied at the peak of the water-evoked hyperpolarization induced cell depolarization which was much larger than that evoked during application of salts to cells bathed in Ringer solution.

Acetates↗

Physiological chemoreceptor stimulation decreases enkephalin and substance P in the carotid body.

Neuroactive peptides, including the enkephalins (Met- and Leu-enkephalin; ME, LE) and substance P (SP) are known to be present in the mammalian carotid body, an arterial chemoreceptor organ sensitive to the O2, CO2 and pH levels in blood. The principal parenchymal (type I) cells of the organ, which receive sensory innervation from the carotid sinus nerve (CSN), have been shown to contain both ME and SP; SP is also present in CSN afferent fibers. In the present study, rabbits were exposed in a chamber to a physiological chemoreceptor stimulus (5% O2 in N2) for one hour, then anesthetized during surgical removal of both carotid bodies for later RIA measurement of ME and SP levels in the tissue; control animals were exposed to air in the chamber, but otherwise treated as the hypoxic animals. Both ME and SP levels were significantly reduced (approximately 40%) in the carotid bodies from hypoxic rabbits, compared to their normoxic controls. The results suggest that these neuroactive peptides are released from carotid body elements during physiological stimulation, and consequently may play a role in the transduction of chemosensory information between the type I cells and their apposed afferent terminals.

Anaerobiosis↗

Protein phosphorylation signaling mechanisms in carotid body chemoreception.

Chemotransduction in the carotid body occurs in specialized type I cells and likely involves a complex series of regulated events which culminates in the release of neurotransmitter agents and the excitation of afferent nerve fibers. Previous studies have shown that multiple factors, including the levels of calcium and cyclic nucleotide second messengers, are important regulators of the chemoreceptor transduction cascade in type I cells. In addition, increases in electrical excitability induced in type I cells by chronic exposure to hypoxia are mimicked by agents which elevate intracellular cyclic AMP levels [Stea et al., J Neurosci 1995;15:2192-2202]. These and other findings suggest that protein kinases, and the phosphorylation of specific protein targets are important components of the hypoxic transduction machinery. Moreover, protein kinase-mediated cascades may participate in the well-known physiological adjustments which occur in the carotid body during prolonged stimulation. In the current study, our data demonstrate (1) the presence of specific protein kinases and target phosphoproteins in the carotid body, and also in the morphologically similar small intensely fluorescent cells of the superior cervical sympathetic ganglia. (2) Nitric oxide production and efferent inhibition in the chemosensory tissue is reduced in the presence of the specific tyrosine kinase inhibitor, lavendustin A. (3) Hypoxia-induced catecholamine release from type I cells is inhibited by the protein kinase A antagonist, Rp-cAMPs. And finally (4), exposure to chronic hypoxia up-regulates the expression of the tyrosine kinase, fyn, and an important growth regulatory phosphoprotein, growth associated protein-43 (GAP-43). These findings suggest that second messenger-mediated phosphorylation and dephosphorylation of specific protein targets is a mechanism capable of regulating diverse cellular functions in the carotid body during acute and chronic stimulation.

Animals↗

Nicotinic versus muscarinic binding sites in cat and rabbit carotid bodies.

It has been suggested that acetylcholine (ACh) might play an important role in carotid body chemoreception. However, a unified explanation of the actions of ACh in this organ has been lacking, due in part to the opposite pharmacological effects of this agent on carotid sinus nerve discharge in different animal species, most notably the cat, where ACh is excitatory, versus the rabbit, where it is inhibitory. In the present study, we utilized receptor binding techniques to compare the nicotinic and muscarinic receptor populations in the carotid bodies of these two species. Our results with the nicotinic ligand 125I-alpha-bungarotoxin and the muscarinic ligand 3H-quinuclidinyl benzilate suggest that nicotinic receptors predominate in the cat by a ratio of 2:1, while in the rabbit, a 12:1 ratio favors muscarinic receptors. Our data suggest that the relative numbers of muscarinic and nicotinic receptors in the carotid bodies of these two species determine the excitatory or inhibitory actions of exogenously administered ACh in this chemoreceptor organ.

Acetylcholine↗