Biomedical subjects

S McAdams

Publications and source records attributed to S McAdams.

35 records · Page 2Linked to original sources

PubMed1991

Evidence that potassium channels regulate prolactin secretion in GH4C1 cells by causing extracellular calcium influx.

Tetraethylammonium (TEA), a K+ channel blocker, induced prolactin (PRL) secretion in GH4C1 cells in a dose-dependent manner when applied at a concentration from 1-20 mM. During continuous exposure to TEA, a significant increase in PRL secretion occurred by 20 min and the response was sustained until the end of a 60-min exposure. Blocking Ca2+ influx by employing a Ca(2+)-depleted medium or the Ca2+ channel blocker, nifedipine, prevented induction of PRL secretion by 20 mM TEA. Preincubation of the cells for 10 min with 20 mM TEA did not inhibit PRL secretion induced by thyrotropin-releasing hormone (TRH), phorbol 12-myristate 13-acetate (TPA) or by cell swelling produced by 30% medium hyposmolarity, but significantly depressed that induced by depolarizing 30 mM K+. BaCl2, another K+ channel blocker, had the same effect on PRL secretion as TEA. The data suggest that blocking K+ channels may cause membrane depolarization, thereby inducing Ca2+ influx which is a potent stimulus for PRL secretion in GH4C1 cells.

Calcium↗

PubMed1991

Dual effect of osmotic cell swelling on prolactin secretion by acutely dispersed adenohypophyseal cells.

Cell swelling induced by acute exposure to the permeant molecule urea or by medium hyposmolarity evoked a prompt PRL secretory burst from dispersed rat anterior pituitary cells. However, during continuous exposure greater than or equal to 10 min to these conditions inhibition of basal and TRH-induced PRL secretion occurred and there was an "off" burst of PRL secretion following return to basal conditions. Compared with continuous TRH stimulation which causes biphasic PRL secretion with a rapid high amplitude first phase secretory burst followed by a sustained low level second phase of secretion, cell swelling induced only "first phase" secretion. Removing Ca2+ from the medium or adding 50 microM verapamil markedly depressed the "off" secretory burst following return to basal conditions but had no effect on the initial high amplitude burst. Our data suggest that the effect of cell swelling on PRL secretion is complex and that there are at least two mechanisms for PRL secretion in normal anterior pituitary cells; these are differently affected by cell swelling and Ca2+ influx.

Animals↗

PubMed1991

Segregation of concurrent sounds. II: Effects of spectral envelope tracing, frequency modulation coherence, and frequency modulation width.

The research presented here concerns the simultaneous grouping of the components of a vocal sound source. McAdams [J. Acoust. Soc. Am. 86, 2148-2159 (1989)] found that when three simultaneous vowels at different pitches were presented with subaudio frequency modulation, subjects judged them as being more prominent than when no vibrato was present. In a normal voice, when the harmonics of a vowel undergo frequency modulation they also undergo an amplitude modulation that traces the spectral envelope. Hypothetically, this spectral tracing could be one of the criteria used by the ear to group components of each vowel, which may help explain the lack of effect of frequency modulation coherence among different vowels in the previous study. In this experiment, two types of vowel synthesis were used in which the component amplitudes of each vowel either remained constant with frequency modulation or traced the spectral envelope. The stimuli for the experiment were chords of three different vowels at pitch intervals of five semitones (ratio 1.33). All the vowels of a given stimulus were produced by the same synthesis method. The subjects' task involved rating the prominence of each vowel in the stimulus. It was assumed that subjects would judge this prominence to be lower when they were not able to distinguish the vowel from the background sound. Also included as stimulus parameters were the different permutations of the three vowels at three pitches and a number of modulation conditions in which vowels were unmodulated, modulated alone, and modulated either coherently with, or independently of, the other vowels. Spectral tracing did not result in increased ratings of vowel prominence compared to stimuli where no spectral tracing was present. It would therefore seem that it has no effect on grouping components of sound sources. Modulated vowels received higher prominence ratings than unmodulated vowels. Vowels modulated alone were judged to be more prominent than vowels modulated with other vowels. There was, however, no significant difference between coherent and independent modulation of the three vowels. Differences among modulation conditions were more marked when the modulation width was 6% than when it was 3%.

Attention↗

PubMed1991

Significant qualitative differences exist between thyrotropin and prolactin secretory dynamics induced by pituitary cell swelling.

Cell swelling produced by a variety of techniques is a potent stimulus intensity-related inducer of an immediate secretory burst of thyroid-stimulating hormone (TSH) and prolaction (PRL) secretion from anterior pituitary cells. A 2-min "square wave" exposure to either hyposmolarity or isotonic urea induced stimulus intensity-correlated TSH and PRL secretory bursts peaking within 3 min, but the PRL zenith occurred 1 min later than that of TSH. With continuous exposure to these stimuli, TSH secretion rapidly decreased and remained only slightly above the unstimulated rate after 5 min. PRL secretion fell to and remained below the unstimulated level after 10 min. After stopping the stimulus, another secretory burst ("off" response) occurred with PRL, but not with TSH. A progressive "ramp" increase in stimulus intensity over 18 min induced a corresponding gradual increase in TSH secretion; there was a progressive depression, rather than increase, in PRL secretion during the stimulus ramp, with an off response secretory burst when the stimulus was discontinued. Removal of extracellular Ca2+ or addition of verapamil to the medium did not alter the dynamics of hyposmolarity-induced TSH secretion, but markedly altered those of PRL secretion; there was no off response PRL secretion and a hyposmolar ramp induced a corresponding gradual increase in PRL secretion, with a return to baseline after removing the stimulus. The dramatic qualitative differences in the response of the thyrotroph and lactotroph may reflect differences between the cell types in the size of secretory vesicles, membrane potential, the mechanism of exocytosis, and/or the role of Ca2+ influx across the plasmalemma.

Animals↗

PubMed1991

Quinidine inhibits prolactin secretion induced by thyrotropin-releasing hormone, high medium potassium or hyposmolarity in GH4C1 cells.

In cultured GH4C1 cells quinidine inhibited basal prolactin (PRL) secretion and that induced by 0.1 to 10 nM thyrotropin-releasing hormone (TRH), 30 mM medium K+ or 30% medium hyposmolarity but did not inhibit secretion induced by 100 nM 12-O-tetradecanoylphorbol 13-acetate. Inhibition of basal PRL secretion was highly correlated with the drug concentration between 30 microM to 1 mM quinidine; 50% inhibition of basal secretion occurred at 300 microM and at this concentration quinidine completely blocked PRL secretion stimulated by TRH, K+ and hyposmolarity. Significant inhibition of TRH-induced PRL secretion was produced by 15 microM quinidine, a concentration equivalent to that in plasma during standard antiarrhythmic therapy with quinidine in humans. In rats in vivo, a single injection of 2 mg i.p. of quinidine gluconate/100 g b.wt. 1 hr before TRH injection significantly inhibited induced TSH secretion by 15%. Quinidine inhibition of secretion may be caused by blocking depolarization of the cell membrane, thus depressing voltage-gated Ca++ channels and preventing a rise in intracellular Ca++ release.

Anti-Arrhythmia Agents↗

PubMed1990

The permeant molecule urea stimulates prolactin secretion in GH4C1 cells by inducing Ca2+ influx through dihydropyridine-sensitive Ca2+ channels.

Isotonic urea in medium with a normal 1.2 mM Ca2+ concentration induced a striking rise in both cytosolic Ca2+ concentration ([Ca2+]i) and prolactin (PRL) secretion, each of whose peaks were proportional to the concentration of urea between 5 and 120 mM. There was a significant linear relationship between the peaks of induced [Ca2+]i and PRL secretion (r = 0.99, P less than 0.001). The increase in both [Ca2+]i and PRL secretion was completely abolished by removal of medium Ca2+ or by 2 microM nifedipine. Hypertonic urea was ineffective in inducing either an increase in [Ca2+]i or PRL secretion. These data support the hypothesis that plasma membrane expansion is a potent non-toxic inducer of hormone secretion and that in GH4C1 cells an increase in [Ca2+]i produced by enhanced influx of extracellular Ca2+ through dihydropyridine-sensitive Ca2+ channels plays an important role in this phenomenon.

Animals↗

PubMed1990

Hearing a mistuned harmonic in an otherwise periodic complex tone.

The ability of a listener to detect a mistuned harmonic in an otherwise periodic tone is representative of the capacity to segregate auditory entities on the basis of steady-state signal cues. By use of a task in which listeners matched the pitch of a mistuned harmonic, this ability has been studied, in order to find dependences on mistuned harmonic number, fundamental frequency, signal level, and signal duration. The results considerably augment the data previously obtained from discrimination experiments and from experiments in which listeners counted apparent sources. Although previous work has emphasized the role of spectral resolution in the segregation process, the present work suggests that neural synchrony is an important consideration; our data show that listeners lose the ability to segregate mistuned harmonics at high frequencies where synchronous neural firing vanishes. The functional form of this loss is insensitive to the spacing of the harmonics. The matching experiment also permits the measurement of the pitches of mistuned harmonics. The data exhibit shifts of a form that argues against models of pitch shifts that are based entirely upon partial masking.

Adult↗

PubMed1990

Medium hyposmolarity stimulates prolactin secretion in GH4C1 cells by inducing an increase in cytosolic free calcium.

Extracellular hyposmolarity is a potent direct stimulus for hormone secretion for which a mechanism has not been delineated. The importance of plasmalemma Ca2+ permeability in this phenomenon in pituitary tumor-derived GH4C1 cells was evaluated by comparing the dynamics of changes in cytosolic free Ca2+ concentration [( Ca2+]i) with those of PRL secretion. At a normal physiological concentration of extracellular Ca2+ (1.5 mM), hyposmolarity induced a striking rise in both [Ca2+]i and PRL secretion, which was proportional to the stimulus between 0.50% reduction in medium osmolarity. Thirty percent hyposmolarity induced a 3-fold rise in [Ca2+]i and a 5-fold rise in PRL secretion above the basal level. These effects did not occur in cells incubated in a medium with a Ca2+ concentration lower than 30 microM. In cells incubated in 1.5 mM Ca2+, the Ca2(+)-channel antagonists, nifedipine and verapamil, significantly inhibited hyposmolar-induced increases in [Ca2+]i and PRL secretion. These data suggest that in GH4C1 cells medium hyposmolarity causes a burst of PRL secretion that depends on a similar preceding rise in [Ca2+]i produced by extracellular Ca2+ influx, most of which passes through dihydropyridine-sensitive Ca2(+)-channels.

Animals↗

PubMed1990

Evidence that ethanol induces prolactin secretion in GH4C1 cells by producing cell swelling with resultant calcium influx.

Although acute exposure to ethanol has been reported to affect hormone secretion, the data are sometimes conflicting, and the mechanism of action of ethanol is unclear. We have examined in GH4C1 cells the effect of isotonic ethanol on cell volume measured with a Coulter counter, the cytosolic Ca2+ concentration ([Ca2+]i) monitored with fura-2, and PRL secretion analyzed in a perifusion system. Isotonic ethanol caused prompt cell swelling and an explosive rise in both [Ca2+]i and PRL secretion proportional to the concentration of ethanol between 5-120 mM. The increases in both [Ca2+]i and PRL secretion induced by 80 mM isotonic ethanol were essentially abolished by removal of medium Ca2+ or by nifedipine; the nifedipine IC50 was approximately 20 nM. Cell swelling induced by hyposmolarity or isotonic urea similarly increased both [Ca2+]i and PRL secretion. Hypertonic ethanol did not cause cell swelling and was ineffective in inducing an increase in either [Ca2+]i or PRL secretion. These data suggest that in GH4C1 cells a major mechanism by which ethanol stimulates PRL secretion is to induce cell swelling, thus producing enhanced Ca2+ influx through dihydropyridine-sensitive Ca2+ channels.

Animals↗

PubMed1990

Role of extracellular calcium and calmodulin in prolactin secretion induced by hyposmolarity, thyrotropin-releasing hormone, and high K+ in GH4C1 cells.

The mechanism by which 30% medium hyposmolarity induces PRL secretion by GH4C1 cells was compared with that induced by 100 nmol/l TRH or 30 mmol/l K+. Removing medium Ca2+, blocking Ca2+ channels with 50 mumol/l verapamil, or inhibiting calmodulin activation with 20 mumol/l trifluoperazine, 10 mumol/l chlorpromazine or 10 mumol/l pimozide almost completely blocked hyposmolarity-induced secretion. The smooth muscle relaxant, W-7, which is believed relatively specific in inhibiting the Ca2(+)-calmodulin interaction, depressed hyposmolarity-induced PRL secretion in a dose-dependent manner (r = -0.991, p less than 0.01). The above drugs also blocked or decreased high K(+)-induced secretion, but had much less effect on TRH-induced secretion. Secretion induced by TRH, hyposmolarity, or high K+ was optimal at pH 7.3-7.65 and was significantly depressed at pH 6.0 or 8.0, indicating that release of hormone induced by all 3 stimuli is due to an active cell process requiring a physiologic extracellular pH and is not produced by nonspecific cell toxicity. The data suggest hyposmolarity and high K+ may share some similarities in their mechanism of stimulating secretion, which is different from that of TRH.

Animals↗

PubMed1989

Cell swelling induced by the permeant molecules urea or glycerol induces immediate high amplitude thyrotropin and prolactin secretion by perifused adenohypophyseal cells.

The permeant molecules, urea and glycerol, evoked a prompt secretory burst of TSH and PRL when added to the extracellular medium of acutely dispersed anterior pituitary cells. Secretion of both hormones was proportional to the concentration of urea or glycerol between 26 and 104 mM (r greater than 0.89, P less than 0.001). Equivalent concentrations of the impermeant molecule, mannitol, did not induce secretion. The acute TSH and PRL secretory responses to TRH, hyposmolarity, and permeant molecules were qualitatively indistinguishable. These data support our hypothesis that cell swelling and resultant plasmalemma expansion is a potent inducer of hormone secretion. Since the secretory response to permeant molecules was not reduced in a Ca2+-free medium containing 0.1 mM EGTA, an increase in Ca2+ transport across the plasmalemma to raise cytosol Ca2+ concentration does not appear involved.

Animals↗

PubMed1989

Comparison of isoproterenol and dibutyryl adenosine cyclic 3',5'-monophosphate stimulation of thyroxine 5'-deiodinase activity in cultured pineal glands from euthyroid and hypothyroid rats.

Thyroxine 5'-deiodinase was increased by isoproterenol and dibutyryl adenosine cyclic 3',5'-monophosphate in a dose- and time-related manner in cultured rat pineal gland. Basal and stimulated activity was higher in glands from hypothyroid than from euthyroid animals. Our data suggest direct beta-adrenergic stimulation of intracellular cyclic AMP may be involved in the regulation of pineal thyroxine 5'-deiodinase activity.

Animals↗

PubMed1989

Dichotic perception and laterality in neonates.

Groups of 4-day-old neonates were tested for dichotic discrimination and ear differences with the High-Amplitude-Sucking procedure. In the first experiment, dichotic speech discrimination was attested by comparison with a control group. Furthermore, among those subjects who showed a substantial recovery of sucking response at least after one of the two syllable changes, it was observed that significantly more subjects manifested a stronger reaction to a right-ear change than to a left-ear change. In the second experiment, 4-day-old neonates were tested on syllable and music timbre discrimination. The significant Stimulus Type x Ear interaction observed suggests perceptual asymmetries indicative of very precocious brain specialization.

Arousal↗

PubMed1989

Segregation of concurrent sounds. I: Effects of frequency modulation coherence.

Frequency modulation coherence was investigated as a possible cue for the perceptual segregation of concurrent sound sources. Synthesized chords of 2-s duration and comprising six permutations of three sung vowels (/a/, /i/, /o/) at three fundamental frequencies (130.8, 174.6, and 233.1 Hz) were constructed. In one condition, no vowels were modulated, and, in a second, all three were modulated coherently such that the ratio relations among all frequency components were maintained. In a third group of conditions, one vowel was modulated, while the other two remained steady. In a fourth group, one vowel was modulated independently of the two other vowels, which were modulated coherently with one another. Subjects were asked to judge the perceived prominence of each of the three vowels in each chord. Judged prominence increased significantly when the target vowel was modulated compared to when it was not, with the greatest increase being found for higher fundamental frequencies. The increase in prominence with modulation was unaffected by whether the target was modulated coherently or not with nontarget vowels. The modulation and pitch position of nontarget vowels had no effect on target vowel prominence. These results are discussed in terms of possible concurrent auditory grouping principles.

Acoustic Stimulation↗

PubMed1989

Ontogenesis of pineal thyroxine 5'-deiodinase activity and plasma melatonin concentration in the rat.

Rat pineal thyroxine 5'-deiodinase (5'-D) activity was detectable by 5 days after birth. Nyctohemeral differences became significant by 10 days of age and gradually reached adult magnitude at 1-2 months, primarily due to a progressive increase in nocturnal enzyme activity. A nyctohemeral difference in N-acetyltransferase (NAT) activity was observed by 5 days postnatally and the maturation of NAT rhythmicity was characterized by both a decrease in diurnal and an increase in nocturnal enzyme activity. The maturation of 5'-D rhythmicity was slower than that of NAT. Isoproterenol stimulated 5'-D activity in 5-day-old rats in which there was no spontaneous nyctohemeral 5'-D rhythm, suggesting that the appearance of rhythmicity in pineal 5'-D may depend on the development of pineal innervation. Melatonin was detectable in plasma by 5 days postnatally and reached adult levels at 21 days. A nyctohemeral difference in plasma melatonin concentration existed from day 5 with the highest value at midnight. The difference between noon and midnight increased approximately 10-fold to the adult amplitude by 15 days of age. There was a transient rise of both diurnal and nocturnal plasma melatonin concentration which peaked at 10 days before dropping severalfold to the adult level for both noon and midnight values by 21 days. Since the rhythms of pineal NAT activity and of plasma melatonin concentration are established before that of pineal 5'-D, it is unlikely that the rhythm of melatonin secretion is initiated by a prior maturation of the pineal 5'-D rhythm.

Acetyltransferases↗

PubMed1989

Lidocaine inhibits dispersed anterior pituitary cell thyrotropin and prolactin secretion induced by thyrotropin-releasing hormone or high medium potassium.

Lidocaine at a concentration greater than or equal to 0.1 mM inhibited thyrotropin (TSH) and prolactin (PRL) secretion by perifused acutely dispersed rat adenohypophyseal cells stimulated by 10-100 microM thyrotropin-releasing hormone (TRH) or 30 mM K+. The concentration of lidocaine required for half-maximal inhibition of TSH and PRL secretion was approximately 1 and 0.5 mM, respectively. Maximal lidocaine inhibition of TRH-induced secretion was induced within 15 min and a normal response to these secretagogues returned within 20 min after removal of lidocaine from the perifusion medium. The inhibition of secretion by lidocaine may be caused by blocking depolarization of the cell membrane and depressing intracellular calcium mobilization and calcium influx across the plasma membrane.

Animals↗

PubMed1986

Discrimination of spectral density.

Experiments were performed to determine the ability of human listeners to discriminate between a sound with a large number of spectral components in a band, of given characteristic frequency and bandwidth, and a sound with a smaller number of components in that band. A pseudorandom placement of the components within the band ensured that no two sounds were identical. The data suggested that discrimination is primarily based upon the perception of temporal fluctuations in the intensity of the sound and secondarily upon resolved structure in the spectrum, perceived as tone color. Experiments using clusters of complex harmonic sounds showed that listeners are able to use the information in upper harmonic bands to discriminate spectral density.

Acoustic Stimulation↗