Beta-adrenergic relaxation of dog trachealis: contractile agonist-specific interaction

The phenomenon of contractile agonist-dependent relaxation by isoproterenol (ISO) of active tension elicited by acetylcholine (ACh), histamine (HIS), serotonin (5-HT), and potassium chloride-substituted Krebs-Henseleit solution (KCl) was studied in 210 tracheal smooth muscle (TSM) strips from 28 mongrel dogs in vitro. All TSM strips were contracted to similar active tensions [target tension (TT) = 50% of the maximal active tension elicited by 127 mM KCl] with ACh, HIS, 5-HT, or KCl and relaxed with either ISO, forskolin (FSK), N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP), or 3-isobutyl-1-methylxanthine (IMX). The concentrations of ISO causing 50% relaxation from TT (RC50) were ACh (2.9 +/- 1.1 x 10(-6) M) greater than 5-HT (8.4 +/- 1.5 x 10(-8) M) approximately KCl (8.1 +/- 2.1 x 10(-8) M) greater than HIS (1.6 +/- 0.2 x 10(-8) M). FSK and IMX relaxed TSM in the same rank order of potency as ISO. In contrast to the contractile agonist-dependent relaxation elicited by ISO, FSK, and IMX, db-cAMP was nearly equipotent in relaxing similarly contracted strips. These results are consistent with contractile agonist-specific interaction with cAMP production by ISO and FSK. These data demonstrate that the phenomenon of contractile agonist-dependent relaxation by ISO is not related specifically to the beta-adrenoceptor.     

Extracellular Ca2+ mobilization in potential-dependent contraction of trachealis of maturing swine.

We studied the effect of maturation on potassium-induced parasympathetic activation and Ca2+ entry in tracheal smooth muscle (TSM) from fifteen 2-wk-old (2ws) and sixteen 10-wk-old (10ws) male domestic farm swine. Atropine (10(-7) M) caused inhibition of the maximal contraction elicited by potassium to 50.3 +/- 2.6% maximum of control response (P less than 0.001) in TSM from 2ws but had no significant effect in TSM from 10ws (94.6 +/- 4.2% maximum; P = NS vs. control). Verapamil (10(-7) M) plus 10(-7) M atropine reduced contraction elicited by potassium in both 2ws (23.7 +/- 5.8% maximum; P less than 0.001 vs. control) and 10ws (50.6 +/- 6.3% maximum; P less than 0.001 vs. control, P less than 0.05 vs. 2ws); 10(-6)M verapamil caused greater than 95% blockade of contraction caused by potassium in both 2ws and 10ws. In separate studies, atropine-treated strips were equilibrated with extracellular Ca2+ concentrations ([Ca2+]o) ranging from normal (1X [Ca2+]o) to four times normal (4x [Ca2+]o). Increasing [Ca2+]o increased maximal contractile response in atropine-treated TSM strips from 68.7 +/- 3.8% maximum for 1x [Ca2+]o to 100.8 +/- 4.8% maximum for 4x [Ca2+]o (P less than 0.001) in 2ws. Neither atropine nor [Ca2+]o affected maximal responses of TSM in 10ws (103.5 +/- 3.0% maximum for 1x [Ca2+]o; P = NS vs. control). However, in the presence of atropine and verapamil, 4x [Ca2+]o augmented KCl-elicited contraction of TSM from both 2ws (46.9 +/- 6.3% maximum; P less than 0.01 vs. control) and 10ws (78.6 +/- 2.3% maximum; P less than 0.005 vs. control).(ABSTRACT TRUNCATED AT 250 WORDS)     

Water homeostasis in desert-dwelling horses

This study set out to investigate tolerance of the body water pool to short-term water deprivation in horses and, in particular, to assess whether feral horses from the Namib Desert showed tolerance to dehydration superior to Transvaal. Hydration status was compared in six feral horses from the Namib Desert and in six Boerperd farm horses under conditions of normal hydration and after 72 h of dehydration. Under normal hydration, the two groups did not differ significantly in water intake, plasma sodium and potassium concentrations, plasma osmolality, hematocrit, total plasma protein, body water content, or water turnover (ml.kg-0.82.day-1). The Namib horses were significantly smaller (P less than 0.0001) and turned over 5 liters less water per day than the Boerperd during normal hydration and 4 liters less during dehydration. Increases in plasma sodium concentration after 72 h of dehydration were greater (P less than 0.05) in the Namib horses. It was concluded that horses can easily tolerate water deprivation that results in a 12% reductions in body mass. The feral horses of the Namib desert were not significantly different per unit mass from domestic horses with regard to indexes of total body water content under conditions of normal hydration and after 72 h of dehydration. Their smaller size and, hence, lower water turnover might be mechanisms they use for survival in the Namib Desert.     

Functions and social consequences of infant–adult male interaction in a captive group of lowland gorillas (Gorilla gorilla gorilla)

The functions and social consequences of infant-adult male interaction in a captive group of lowland gorillas were evaluated. The two males repeatedly attempted to interact with the infant, the infant sometimes attempted to interact with the males, and the mother usually interrupted interactions between male and infant. Infant-directed actions by the two males frequently showed their interest in the infant and infrequently showed care giving toward her; their other infant-directed actions occurred near the time of excitement or of playful actions between adults. Male-directed actions by the infant frequently showed its interest in one male and infrequently showed care seeking from him. All infant-adult male interactions but one occurred in the less stimulating of the gorillas' two enclosures. Boredom and the mother's frequent thwarting of contact between a male and infant are suggested as influences on the males' interest in the infant. The data suggest that availability of interesting objects alleviated the boredom of captivity for males and thus dissuaded them from seeking stimulation which sometimes resulted in harmful behaviors toward the infant.     

Binding of a calcium sensitizer, bepridil, to cardiac troponin C. A fluorescence stopped-flow kinetic, circular dichroism, and proton nuclear magnetic resonance study

Stopped-flow fluorescence kinetic measurements, circular dichroism (CD), and 1H nuclear magnetic resonance (NMR) spectroscopy at 360 MHz have been used to study the interaction of the calcium-channel blocker and calmodulin antagonist bepridil with cardiac troponin C (cTnC) in the presence of calcium. The kinetic data show that bepridil reduces the rate of calcium release only from the low affinity, calcium-specific site and not from the two high affinity calcium/magnesium sites. CD measurements indicate that drug binding leads to a small increase in the alpha-helical content of the complex. 1H NMR shows that the protein binds one equivalent of bepridil, with a dissociation constant of approximately 20 microM, only when the low affinity calcium site is occupied. Exchange is fast or intermediate on the chemical shift time scale. Drug binding is shown to be largely localized in the N-terminal domain, containing the low affinity calcium site, by observing the shifting and broadening of several resonances associated with that domain. These include assigned aromatic signals together with methionyl and other methyl signals. Observation of intermolecular nuclear Overhauser effects was precluded by extensive spectral overlap. Consideration of the data from the three techniques permitted a model of the bepridil-cTnC complex to be constructed, using the model of cTnC derived from the x-ray structure of calmodulin (MacLachlan L. K., Reid, D. G., and Carter, N. (1990) J. Biol. Chem. 265, 9754-9763). Binding of bepridil to a prominent hydrophobic depression in the N-terminal domain can be invoked to explain many of the induced changes in the spectral and kinetic properties of the protein. The implications of the model for the calcium sensitizing action of bepridil are discussed.     

Cytohistologic correlation of peritoneal washing cytology in gynecologic disease

The peritoneal washings and cul de sac aspirates from 204 patients undergoing 217 procedures for the evaluation of gynecologic disease were examined retrospectively and correlated with the histologic diagnoses. Of the 73 washings from patients with histologically benign genital disease, cytology diagnosed 64 (87.7%) as negative, 6 (8.2%) as inconclusive and 3 as malignant. One malignant washing was a true positive from a nongenital primary. False positives thus occurred in 2.7% of the benign cases on blind review. Of 144 cytologic examinations of washings from patients with histologically confirmed malignant disease of the female genital tract, 38 (26.4%) were considered positive after cytohistologic correlation. Four malignant cases (2.1%) were undercalled on blind review while 3 (2.0%) were considered overcalls. Eleven of 47 cases (23.4%) with biopsy-proven peritoneal disease had negative cytology after histologic correlation. Recurring problems in interpreting peritoneal washings included: (1) the differential diagnosis of the spectrum encompassed by reactive mesothelium, endosalpingiosis, borderline serous tumors and well-differentiated serous cystadenocarcinoma; (2) morphologic similarities between some tumor cells and mesothelial cells associated with treatment effects; and (3) a paucity of malignant cells in some washings, resulting in false-negative interpretations. Ineffective cytopreparation, particularly of bloody specimens, hampered interpretation of some specimens. Correlation with previous histology and cytology enhanced the accuracy of peritoneal washing cytology in this study.