Relationship between potency of L-isoprenaline and β-adrenoceptor density estimated in single cells from tracheal smooth muscles of guinea pigs of different ages

1992 ◽  
Vol 70 (4) ◽  
pp. 458-461 ◽  
Author(s):  
Issei Takayanagi ◽  
Mitsutoshi Satoh ◽  
Noriko Kokubu ◽  
Teruko Kato

An age-related change in potency of L-isoprenaline in the presence of ascorbic acid, desmethylimipramine, corticosterone, pargyline, and phentolamine was obtained in tracheal strips from guinea pigs of differing ages between 6 and 40 weeks. The potency in the strips from 100-week-old guinea pigs did not significantly differ from that in strips from 40-week-old animals. Single cells were prepared from the tracheal muscles of 6-, 10-, 40-, and 100-week-old guinea pigs. The specific binding of [3H]dihydroalprenolol to the single cells was saturable. The dissociation constants of [3H]dihydroalprenolol were in good agreement with those of the membrane fractions from the guinea-pig tracheal muscles, and did not change with age. An excellent relationship between the potency of L-isoprenaline and the maximum binding of [3H]dihydroalprenolol estimated in the preparations from 6- to 40-week-old guinea pigs was found, suggesting that the increase in the potency of L-isoprenaline is due to the increase in the maximum binding or receptor density. The value in the preparations from 100-week-old guinea pigs deviated significantly from the regression line. This suggests the possibility that the decrease in potency in the strips from 100-week-old animals is due to a change in post β-receptor processes in responsiveness.Key words: guinea-pig trachea, single cells, β-receptor density, ageing, dissociation constant.

1993 ◽  
Vol 264 (4) ◽  
pp. G624-G629 ◽  
Author(s):  
J. Ishizuka ◽  
M. Murakami ◽  
G. A. Nichols ◽  
C. W. Cooper ◽  
G. H. Greeley ◽  
...  

Gallbladder (GB) motility diminishes with aging. This study was performed to characterize mechanisms that are involved in changes in GB contractility that occur during aging. Cytoplasmic Ca2+ concentrations ([Ca2+]i) and the contractile force of guinea pig GB muscle strips were simultaneously measured using fura-2 and force-displacement transducers. The binding ability of the Ca2+ channel antagonist and GB muscle compliance were also examined. The COOH-terminal octapeptide of cholecystokinin (CCK-8) evoked a dose-dependent increase in force and [Ca2+]i. Changes of [Ca2+]i and contractile force of muscle strips in response to CCK-8 were significantly greater in young (2 mo old) compared with mature and aged (12 and 24 mo old) guinea pigs (changes in [Ca2+]i, ED50: 46.1 nM at 2 mo, 6.1 microM at 12 mo, and 2.8 mM at 24 mo; changes of contractile force, ED50: 24.8 microM at 2 mo, 2.1 mM at 12 mo, and 357 mM at 24 mo). However, the magnitude of the contraction at each percent change in [Ca2+]i was actually similar in young and aged guinea pigs. In a Ca(2+)-free buffer, the responses of [Ca2+]i and force to CCK-8 in both young and aged GB muscles decreased, but those were still dose and age dependent. Binding ability of the Ca2+ channel antagonist did not differ in the young and aged groups, but the compliance of the GB muscle strip decreased with aging. These results suggest that both a reduced mobilization of intracellular Ca2+ and a decreased muscle compliance are responsible, at least in part, for age-related reduced contraction of guinea pig GB in response to CCK.


2002 ◽  
Vol 103 (s2002) ◽  
pp. 345S-348S ◽  
Author(s):  
Angela C. D'APRILE ◽  
Lynette B. FERNANDES ◽  
Paul J. RIGBY ◽  
Roy G. GOLDIE

We examined the impact of parainfluenza-3 (P-3) respiratory tract viral infection on the density and function of endothelin (ET) receptor subtypes (ETA and ETB) in guinea pig tracheal smooth muscle. Total specific binding of [125I]ET-1 and the relative proportions of ETA and ETB binding sites for this ligand were assessed at day 0 (control) and at 2, 4, 8 and 16 days post-inoculation. At day 0, the proportions of ETA and ETB binding sites were 30% and 70% respectively. Total specific binding was significantly reduced at day 4 post-inoculation (32% reduction, n = 8–12, P<0.05) and was largely due to a corresponding fall in ETB receptor density at this time point (38% reduction, n = 8–12, P<0.05). The density of ETA receptors also fell significantly at day 8 post-inoculation (33% reduction, n = 6–12, P<0.05). By day 16 post-inoculation, the densities of ETA and ETB receptors had recovered to control values. The ratio of ETA:ETB receptor subtypes did not alter with P-3 infection. While P-3 infection reduced the density of tracheal smooth muscle ETA and ETB receptors, the contractile sensitivity and maximum response to carbachol and ET-1 was not altered in tissue from day 4 post-inoculation compared with the control. There seems to be a significant functional reserve for both receptor subtypes in this species that buffers the impact of P-3 infection on airway smooth muscle responsiveness to ET-1.


1910 ◽  
Vol 12 (2) ◽  
pp. 151-175 ◽  
Author(s):  
John Auer ◽  
Paul A. Lewis

1. By an immediate anaphylactic reaction we mean the chain of symptoms which occur in highly sensitized guinea-pigs shortly after an intravenous or intracardiac injection of the toxic dose and usually end in death. 2. Immediate anaphylactic death occurs three to five minutes after the toxic injection in highly sensitized guinea-pigs. 3. Immediate anaphylactic death in guinea-pigs is caused by asphyxia; cessation of respiration is secondary to this asphyxia. 4. This asphyxia is apparently produced by a tetanic contraction of the smooth muscles of the bronchioles, which occludes their lumen gradually, so that finally no air enters or leaves the lung, in spite of violent respiratory efforts; the animal is strangulated. 5. The stage of complete broncho-constriction is preceded by a short broncho-dilatation, if the bronchioles have been in a state of tonus previous to the injection of the toxic dose. 6. Anatomically, the lungs of these guinea-pigs are typical and may be used as an indicator of the immediate anaphylactic state when the animal has been immobilized by curarin or by pithing. 7. The lungs of a guinea-pig killed by immediate anaphylaxis are distended and in an inspiratory position so that the diaphragm is pushed down; no marked collapse occurs when the chest is opened and when the lungs are excised in toto; their color is a pale bluish-pink ; the surfaces and borders are smooth; no foam is in the trachea or large bronchi; pieces of lung cut off do not collapse, float lightly on water, and contain a good amount of air and little fluid which escapes on pressure. The blood in the lungs and heart is black when the autopsy is made at once after the cessation of respiration. 8. Section of the vagi in the neck, or curarin (artificial respiration) exerts no appreciable effect on the development of immediate anaphylaxis. 9. This immobilization of the lungs, which is due to a broncho-constriction, is of peripheral origin, for destruction of the spinal cord and medulla affects in no appreciable way the promptness and extent of the typical lung response to the injection of the toxic dose. Artificial respiration is, of course, necessary. At the present time we do not care to state whether the toxic dose exerts its effects upon the bronchial muscles alone or upon the vagus motor endings or upon both structures. 10. The blood pressure in immediate anaphylaxis first shows a rise, which may be considerable; a short maintenance of this high level and then a gradual drop to IO to 20 millimeters of mercury and even less, within ten minutes after injection of the toxic dose. 11. Shortly after injection of the toxic dose a heart block develops, so that auricles and ventricles may beat in a 3:I rhythm; the block is probably due to asphyxia. 12. The cardiac vagus gradually loses its irritability after injection of the toxic dose. 13. Cooling of the guinea-pig delays the reaction to the toxic injection.


2002 ◽  
Vol 119 (1) ◽  
pp. 93-104 ◽  
Author(s):  
Theodor V. Burdyga ◽  
Susan Wray

Moderate cooling of smooth muscle can modulate force production and may contribute to pathophysiological conditions, but the mechanisms underlying its effects are poorly understood. Interestingly, cooling increases force in rat ureter, but decreases it in guinea pigs. Therefore, this study used ureteric smooth muscle as a model system to elucidate the mechanisms of the effects of cooling on excitation-contraction coupling. Simultaneous recordings of force, intracellular [Ca2+], and electrical activity were made in intact ureter and ionic currents measured in isolated cells. The increase in force amplitude in rat ureter with cooling was found to be due to a significant increase in the duration of the Ca2+ transient. This in turn was due to a marked prolongation of the action potential. In guinea pigs, both these parameters were much less affected by cooling. Examination of membrane currents revealed that differences in ion channel contribution to the action potential underlie these differences. In particular, cooling potentiated Ca2+-activated Cl− currents, which are present in rat but not guinea pig ureteric smooth muscle, and prolonged the plateau of the action potential and Ca2+ entry. The force-Ca2+ relationship revealed that the increased duration of the Ca2+ transient was sufficient in the rat, but not in the guinea pig, to overcome kinetic lags produced in both species by cooling and potentiate force. Ca2+ entry and release processes were largely temperature-insensitive, but the rate of relaxation was very temperature-sensitive. Effects of cooling on myosin light chain phosphatase, confirmed in experiments using calyculin A, appear to be the predominant mechanisms affecting relaxation. Thus, smooth muscle is diverse in its response to temperature, even when experimental variables, such as the mode of stimulation, are removed. Although the biochemical and mechanical events accompanying contraction are likely to be affected in similar ways by temperature, differences in electrical events lead to subsequent differences in these processes between smooth muscles.


2020 ◽  
Vol 10 (6) ◽  
pp. 365
Author(s):  
Roger J. Mullins ◽  
Su Xu ◽  
Jiachen Zhuo ◽  
Steve Roys ◽  
Edna F.R. Pereira ◽  
...  

This study used in vivo magnetic resonance imaging (MRI) to identify age dependent brain structural characteristics in Dunkin Hartley guinea pigs. Anatomical T2-weighted images, diffusion kurtosis (DKI) imaging, and T2 relaxometry measures were acquired from a cohort of male guinea pigs from postnatal day (PND) 18–25 (juvenile) to PND 46–51 (adolescent) and PND 118–123 (young adult). Whole-brain diffusion measures revealed the distinct effects of maturation on the microstructural complexity of the male guinea pig brain. Specifically, fractional anisotropy (FA), as well as mean, axial, and radial kurtosis in the corpus callosum, amygdala, dorsal-ventral striatum, and thalamus significantly increased from PND 18–25 to PND 118–123. Age-related alterations in DKI measures within these brain regions paralleled the overall alterations observed in the whole brain. Age-related changes in FA and kurtosis in the gray matter-dominant parietal cerebral cortex and dorsal hippocampus were less pronounced than in the other brain regions. The regional data analysis revealed that between-age changes of diffusion kurtosis metrics were more pronounced than those observed in diffusion tensor metrics. The age-related anatomical differences reported here may be important determinants of the age-dependent neurobehavior of guinea pigs in different tasks.


1968 ◽  
Vol 46 (3) ◽  
pp. 441-448 ◽  
Author(s):  
Sang Whay Kooh ◽  
Donald Fraser

Antiserum to bovine parathyroid hormone (Anti-PTH) was produced in guinea pigs by repeated subcutaneous injections of purified bovine PTH with Freund's adjuvant. Specific binding of PTH with Anti-PTH was demonstrated in vitro by a two-antibody system. Anti-PTH was administered intravenously to three species of animals. Within 8 h, rats had developed a decrease in plasma calcium and an increase in plasma phosphorus concentrations, physiological changes characteristic of the PTH deficiency state. A similar degree of hypocalcemia occurred in rabbits. Some of the animals injected with Anti-PTH died within 24 h; in survivors, the hypoparathyroid state was transient and recovery occurred within 24 h. Equivalent amounts of Anti-PTH had no effect on the levels of plasma calcium in normal guinea pigs. Injections of parathyroid extract to rats, rabbits, and guinea pigs caused a hypercalcemic response. Since antibodies produced in the guinea pig to bovine PTH neutralized the physiological action of rat and rabbit PTH, but did not neutralize that of guinea pig PTH, it is concluded that bovine, rat, and rabbit PTH are immunologically similar, but that guinea pig PTH is dissimilar. However, the hormones of all four species have a common attribute that determines biological activity.


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