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Signal transduction mechanisms mediating secretion in goldfish gonadotropes and somatotropes
s2
PL5
Human auditory perception studied in owls. Masakazu Konishi Division of Biology 2 16-79, California Institute of Technology, Pasadena, CA 9 1125 Models of human auditory perception that use neural data from animals implicitly assume that the same perceptual phenomenon occurs in humans and the animals and that the same neural mechanisms underlie the perceptual phenomenon in both species. Experiments show that humans and owls use similar behavioral methods and neural mechanisms for sound localization. Both species cross-correlate binaural signals to derive interaural time differences for localization in the horizontal plane. Since cross-correlation of periodic signals such as tones produces more than one maximum, both humans and owls fail to distinguish the true sound source from illusory ones in localizing narrow-band signals. This problem of phase ambiguity does not occur with broadband signals in both species, because cross-correlation of these signals gives rise to a single maximum. In owls, the mechanisms of both cross-correlation and the resolution of phase-ambiguity are understood at the level of single neurons. Correlation of left ear and right ear signals is a prerequisite for binaural cross-correlation. As binaural signals are systematically de-correlated, humans perceive progressively blurred images of the sound source. The consistency of localizing sound sources declines with the degree of decorrelation in the same manner in both species. In owls, the neural mechanisms of this phenomenon are understood. PL6
SYMPOSIA Symposium 1: Comparative aspects of hormone receptors and signal transduction. Chair: J.k? Chang (Canada) Sl-1
Signal transduction mechanisms mediating secretion in goldfish gonadotropes and somatotropes. Chang JP, Johnson JD, Van Goor F, Wong CJH, Yunker WK, Jobin RM, Wong AOL and Goldberg JI Department of Biological Sciences, University of Alberta, Edmonton, Alberta, CANADA, T6G 2E9. In goldfish, two gonadotropin-releasing hormones (GnRHs), salmon (s)GnRH and chicken (c)GnRH-II directly stimulate maturational gonadotropin (GTH-II; LH-like) and growth hormone (GH) secretion. GTH-II and GH release in goldfish is a useful model for comparing the signaling mechanisms of two closely related GnRH peptides. sGnRH- and cGnRH-IIinduced hormone secretion in both cell-types share some pathways (involvement of extracellular Ca2+, voltage-sensitive Ca2+ channels, protein kinase C, calmodulin and Na+/H+ antiport, and insensitivity to thapsigargin) but differences also exist. Compared to cGnRH-II, sGnRH action on GTH-II release is less dependent on extracellular Ca2+ and involves an additional arachidonic acid (AA)-dependent pathway. On the other hand, GH responses to both GnRHs are equally sensitive to manipulation of extracellular Ca2+ and independent of AA. Spatiotemporal [Caz+]i changes, and the involvement of nonthapsigargin-sensitive Ca2+ stores, show cell-type- and GnRHspecific characteristics. The ability of the two GnRHs to alter InsP3 levels in goldfish pituitary cell cultures also differs. These findings suggest that the two GnRHs utilize similar, as well as unique, receptor-transduction coupling mechanisms, some aspects of which are distinct from those characterized in mammalian pituitary cells. (Supported by NSERC and AHFMR.)
Surviving hypoxia without really dying. R.G. Boutilier Dept. of Zoology, Univ of Cambridge, UK, CB2 3EJ. Although anaerobic ATP production can temporarily meet the sustained energy demands of various cellular ATP consuming processes, finite stores of fermentable substrate together with the accumulation of deleterious end products (e.g. H+), normally set temporal constraints on anaerobiosis as a long term solution to severe oxygen limitation in animals. One obvious way to forestall the potentially lethal effects of a compromised metabolism would be to lower the energetic demands of one or more of the major ATP consuming functions, and to counter-balance such energetic economies with proportional reductions in ATP production. This strategy of ‘metabolic arrest’ is gainfully employed by several ‘facultative’ vertebrate anaerobes who use anaerobic metabolism not to maintain pre-existing rates of ATP production but to sustain suppressed rates of energy turnover in 02-deprived states. The net effect of this balanced
reduction of ATP supply and demand is that it spares fermentable fuel, reduces metabolic waste accumulation and extends survival time. Cell death caused by O,-lack begins when anaerobic ATP production fails to meet the energetic maintenance demands of ionic and osmotic equilibrium. The resulting Ca’+-mediated sequence of pathological events leading to anoxic cell death is the same in hypoxia-tolerant and hypoxia-sensitive cells, the difference being that the time course of cellular ATP depletion in the former is metered in hours or days and in the latter in minutes. Cell survival during severe hypoxia is therefore not attributable to any superior capacity for hypoxia-tolerant cells to withstand major ionic disruptions or sustained energy imbalances. Instead, the key to their survival lies with their ability to initiate mechanisms which actively suppress ATP synthesis in synchrony with ATP demand in a way that preserves the ionic integrity of cell membranes.
Sl-4
Cytokine regulation of macrophage antimicrobial functions in teleosts M., Dept. Biological Sciences, University of Alberta, Edmonton, AB Canada T6G 2E9 Macrophages are central cells in host defense against pathogens, that are induced to became potent killer cells following activation by cytokines. Relatively little is known about teleost macrophage hematopoiesis and the regulation of their function by cytokines. We characterized teleost macrophage subpopulations and examined their responses to fish cytokines at the population and single-cell level. Different sub-populations of activated teleost macrophages produce potent toxic molecules, the reactive oxygen (ROI) and nitrogen (NRI) intermediates, which are responsible for demise of the invading pathogens. The mechanisms of induction and regulation of ROI and RNI of teleost macrophages differ from those of mammals. Activated teleost macrophages exhibit sequential down-regulation of antimicrobial responses, in the absence of external stimuli. This self-regulation of the expression of effector molecules by teleost macrophages may significantly decrease the tissue damage at the sites of inflammation, and optimize the ability of teleost macrophages to defend against different pathogens.
PL5
Human auditory perception studied in owls. Masakazu Konishi Division of Biology 2 16-79, California Institute of Technology, Pasadena, CA 9 1125 Models of human auditory perception that use neural data from animals implicitly assume that the same perceptual phenomenon occurs in humans and the animals and that the same neural mechanisms underlie the perceptual phenomenon in both species. Experiments show that humans and owls use similar behavioral methods and neural mechanisms for sound localization. Both species cross-correlate binaural signals to derive interaural time differences for localization in the horizontal plane. Since cross-correlation of periodic signals such as tones produces more than one maximum, both humans and owls fail to distinguish the true sound source from illusory ones in localizing narrow-band signals. This problem of phase ambiguity does not occur with broadband signals in both species, because cross-correlation of these signals gives rise to a single maximum. In owls, the mechanisms of both cross-correlation and the resolution of phase-ambiguity are understood at the level of single neurons. Correlation of left ear and right ear signals is a prerequisite for binaural cross-correlation. As binaural signals are systematically de-correlated, humans perceive progressively blurred images of the sound source. The consistency of localizing sound sources declines with the degree of decorrelation in the same manner in both species. In owls, the neural mechanisms of this phenomenon are understood. PL6
SYMPOSIA Symposium 1: Comparative aspects of hormone receptors and signal transduction. Chair: J.k? Chang (Canada) Sl-1
Signal transduction mechanisms mediating secretion in goldfish gonadotropes and somatotropes. Chang JP, Johnson JD, Van Goor F, Wong CJH, Yunker WK, Jobin RM, Wong AOL and Goldberg JI Department of Biological Sciences, University of Alberta, Edmonton, Alberta, CANADA, T6G 2E9. In goldfish, two gonadotropin-releasing hormones (GnRHs), salmon (s)GnRH and chicken (c)GnRH-II directly stimulate maturational gonadotropin (GTH-II; LH-like) and growth hormone (GH) secretion. GTH-II and GH release in goldfish is a useful model for comparing the signaling mechanisms of two closely related GnRH peptides. sGnRH- and cGnRH-IIinduced hormone secretion in both cell-types share some pathways (involvement of extracellular Ca2+, voltage-sensitive Ca2+ channels, protein kinase C, calmodulin and Na+/H+ antiport, and insensitivity to thapsigargin) but differences also exist. Compared to cGnRH-II, sGnRH action on GTH-II release is less dependent on extracellular Ca2+ and involves an additional arachidonic acid (AA)-dependent pathway. On the other hand, GH responses to both GnRHs are equally sensitive to manipulation of extracellular Ca2+ and independent of AA. Spatiotemporal [Caz+]i changes, and the involvement of nonthapsigargin-sensitive Ca2+ stores, show cell-type- and GnRHspecific characteristics. The ability of the two GnRHs to alter InsP3 levels in goldfish pituitary cell cultures also differs. These findings suggest that the two GnRHs utilize similar, as well as unique, receptor-transduction coupling mechanisms, some aspects of which are distinct from those characterized in mammalian pituitary cells. (Supported by NSERC and AHFMR.)
Surviving hypoxia without really dying. R.G. Boutilier Dept. of Zoology, Univ of Cambridge, UK, CB2 3EJ. Although anaerobic ATP production can temporarily meet the sustained energy demands of various cellular ATP consuming processes, finite stores of fermentable substrate together with the accumulation of deleterious end products (e.g. H+), normally set temporal constraints on anaerobiosis as a long term solution to severe oxygen limitation in animals. One obvious way to forestall the potentially lethal effects of a compromised metabolism would be to lower the energetic demands of one or more of the major ATP consuming functions, and to counter-balance such energetic economies with proportional reductions in ATP production. This strategy of ‘metabolic arrest’ is gainfully employed by several ‘facultative’ vertebrate anaerobes who use anaerobic metabolism not to maintain pre-existing rates of ATP production but to sustain suppressed rates of energy turnover in 02-deprived states. The net effect of this balanced
reduction of ATP supply and demand is that it spares fermentable fuel, reduces metabolic waste accumulation and extends survival time. Cell death caused by O,-lack begins when anaerobic ATP production fails to meet the energetic maintenance demands of ionic and osmotic equilibrium. The resulting Ca’+-mediated sequence of pathological events leading to anoxic cell death is the same in hypoxia-tolerant and hypoxia-sensitive cells, the difference being that the time course of cellular ATP depletion in the former is metered in hours or days and in the latter in minutes. Cell survival during severe hypoxia is therefore not attributable to any superior capacity for hypoxia-tolerant cells to withstand major ionic disruptions or sustained energy imbalances. Instead, the key to their survival lies with their ability to initiate mechanisms which actively suppress ATP synthesis in synchrony with ATP demand in a way that preserves the ionic integrity of cell membranes.
Sl-4
Cytokine regulation of macrophage antimicrobial functions in teleosts M., Dept. Biological Sciences, University of Alberta, Edmonton, AB Canada T6G 2E9 Macrophages are central cells in host defense against pathogens, that are induced to became potent killer cells following activation by cytokines. Relatively little is known about teleost macrophage hematopoiesis and the regulation of their function by cytokines. We characterized teleost macrophage subpopulations and examined their responses to fish cytokines at the population and single-cell level. Different sub-populations of activated teleost macrophages produce potent toxic molecules, the reactive oxygen (ROI) and nitrogen (NRI) intermediates, which are responsible for demise of the invading pathogens. The mechanisms of induction and regulation of ROI and RNI of teleost macrophages differ from those of mammals. Activated teleost macrophages exhibit sequential down-regulation of antimicrobial responses, in the absence of external stimuli. This self-regulation of the expression of effector molecules by teleost macrophages may significantly decrease the tissue damage at the sites of inflammation, and optimize the ability of teleost macrophages to defend against different pathogens.