Cholesteryl hemisuccinate alters membrane fluidity, angiotensin receptors, and responses in adrenal glomerulosa cells

We examined the effects of cholesteryl hemisuccinate on membrane fluidity and angiotensin II (AII) actions in bovine adrenal glomerulosa cells. Incubating cells with cholesteryl hemisuccinate decreased membrane fluidity and markedly inhibited AII binding. The effect on binding was characterized by a decrease in AII receptor number. The effects of AII on phosphatidyl inositol turnover and calcium fluxes, proposed intermediaries of AII actions on aldosterone secretion, were less impaired than AII binding by cholesteryl hemisccinate. AII stimulation of aldosterone secretion was preserved despite the decrease in AII binding after cholesteryl hemisuccinate treatment. These results indicate that AII binding can be dissociated from its effects on aldosteronogenesis by a reagent that alters membrane fluidity.     

Effect of Some Calcium Antagonists on Muscarinic Receptor-Mediated Cyclic GMP Formation

Several calcium antagonists were screened for their effect on muscarinic acetylcholine receptor-mediated cyclic GMP formation in murine neuroblastoma cells (clone N1E-115). Mn2+, Ni2+, and verapamil rapidly antagonized the response noncompetitively, with the following order of potency: verapamil greater than Mn2+ greater than Ni2+. The effects of Mn2+ and Ni2+, but not those of verapamil, were largely reversed by increasing extracellular calcium concentration. Additional effects of these agents included displacement of [3H]quinuclidinyl benzilate binding by verapamil and elevation of cyclic GMP levels by Mn2+ and Ni2+ in the absence of agonists. These results are in support of the hypothesis that receptor-mediated cyclic GMP formation by these cells is dependent upon entry of calcium into the cell and demonstrate the complexity of the effects of calcium antagonists.     

Calmodulin-binding drugs affect responses to cytokinin, auxin, and gibberellic Acid

Trifluoperazine, a phenothiazine tranquilizer, and tetracaine, a local anesthetic, have been found to inhibit a variety of plant hormone responses at concentrations compatible with their known inhibition of Ca²⁺-calmod-ulin-dependent enzyme activities. Among these responses are cytokinin-dependent betacyanin synthesis and increase in fresh weight in Amaranthus tricolor cotyledons, auxin-dependent increase in length of wheat coleoptile segments and gibberellic acid-dependent induction of α-amylase synthesis in barley aleurone layers. The reversibility of some of these inhibitory effects has been demonstrated, indicating that, up to a point, a generalized membrane destruction can be ruled out. The evidence, taken in conjunction with numerous examples from the literature showing calcium involvement in the action of all of the plant hormones, support a unifying theory of hormone action.     

24-hour variation in content and release of hypothalamic neuropeptides in the rat

The tissue content of up to eight neuropeptides, viz bombesin (BOM), cholecystokinin (CCK-8), neurotensin (NT), neuropeptide Y (NPY), peptide histidine isoleucine amide (PHI), somatostatin (SRIF), substance P (SP) and vasoactive intestinal polypeptide (VIP), in rat hypothalami removed at various times of the day, was measured using specific radioimmunoassays. There was significant variation in the content of BOM, CCK-8, NT, PHI, SP and VIP across a 24-h period. The levels of BOM, CCK-8 and NT were lowest around the onset of darkness (1900 h) and rose throughout the night to reach a peak around the time of lights on. Hypothalamic content of all eight peptides fell between 0700 h and 1300 h by an average of 45 +/- 4%. Basal release of these peptides, as well as that in the presence of 48 mM potassium (K+), was measured from hypothalami removed between 0700 and 1900 h and incubated in vitro in a CSF-like medium. Basal secretion of NT significantly increased, whilst that of CCK-8 significantly decreased over the same period. There was no significant change in the basal release of the other neuropeptides. The release in the presence of 48 mM K+ of SP decreased significantly during the day, whilst that of VIP significantly increased. There was also a significant change in the stimulated release of BOM, levels falling during the morning and rising again at 1900 h. 48 mM K+ caused a significant increase in the release of SRIF and SP at all times tested. Whilst 48 mM K+ induced a significantly higher release of CCK-8 and NT in the morning, this stimulus was ineffective in the evening. The contrary was true in the case of BOM, NPY and VIP, where a significant stimulation was induced only at 1900 h. The possible implications of these findings are discussed.     

Dose-response comparisons of canine plasma gastroenteropancreatic hormone responses to bombesin and the porcine gastrin-releasing peptide (GRP)

This study compares the potencies of the porcine gastrin-releasing peptide (pGRP) and bombesin, in causing elevations of canine plasma gastroenteropancreatic (GEP) levels. In the dose range 0-600 pmol . kg-1 . h-1, infusion of both peptides resulted in obvious dose-related elevations of plasma levels of gastrin, pancreatic polypeptide, enteroglucagon, immunoreactive pancreatic glucagon, and insulin. In this dose range, no significant difference in potency between the two peptides in elevating plasma levels of the above hormones was observed. The results of this study, demonstrating equimolar potency of pGRP and bombesin, are in contrast to previous studies reporting that pGRP was less potent than bombesin in causing certain bioactivities in the rat following intracranial administration of the two peptides.     

VARIATION IN THE DURATION OF MITOSIS IN THE CRYPTS OF LIEBERKUHN OF THE RAT; A CYTOKINETIC STUDY USING VINCRISTINE

The variation in the duration of mitosis ( t _m) with cell position in the small intestinal crypts of the adult rat has been measured by a stathmokinetic technique using vincristine. The value for the whole crypt column was 0.43 hr, or 26 min. At the bottom of the crypt t _m was in excess of 1 hr, but rapidly decreased and throughout the greater part of the proliferative compartment was between 0.40 and 0.50 hr. At the top of the proliferative compartment an increase in t _m was demonstrated.
If the value of 0.43 hr for the whole crypt column is correct, then one argument for postulating the formation of metabolic DNA during differentiation in the small bowel epithelium of the rat becomes invalid. Variations in t _m within the crypt have been shown to increase the values of cell velocity obtained from cumulative birth rate diagrams. Finally further evidence has been presented for the existence of a slowly dividing subpopulation of cells at the base of the crypt. These cells may be important in crypt repopulation after damage with phase specific anti-tumour drugs.     

Bile acids XLII. Preparation of 5-alpha-cholestan-26-oic acids from kryptogenin

3β, 7α, 26-Triacetoxy-5α-cholestane was prepared from 25R-3β, 26-diacetoxy-5α-cholestan-7α-ol, and partially hydrolyzed with potassium carbonate in methanol-benzene. The three acetylated products thus obtained were characterized by thin layer and gas liquid chromatography, and mass spectrometry. By oxidation and alkaline hydrolysis, 3β, 7α-diacetoxy-5α-cholestan-26-ol was converted to 3β, 7α-dihydroxy-5α-cholestanoic acid. 7α, 26-Diacetoxy-5α-cholestan-3β-ol was characterized as indicated. The third product, 7α-acetoxy-5α-cholestane-3β, 26-diol was oxidized to 3-oxo-7α-acetoxy-5α-cholestanoic acid which was reduced catalytically and hydrolyzed to provide 3α, 7α-dihydroxy-5α-cholestanoic acids and its 3β-isomer. By comparison of the specific rotation of this sample of 3α, 7α-dihydroxy-5α-cholestanoic acid derived from 25R-kryptogenin with a similar product derived from arihydro-5α-cyprinol obtained from carp bile, the latter derivative appears to be primarily the 25S material.     

Factors Influencing the Onset of Chronic Respiratory Disease

To investigate the effect of different environmental and personal factors on ventilatory function 10,971 children resident and going to school in four areas of Kent were examined. Details of past respiratory illnesses were obtained by a questionary completed by the parents; the examination included measurement of height, weight, and peak expiratory flow.Area of residence, social class, family size, and a past history of pneumonia, bronchitis, or asthma were found to be associated with differing levels of peak expiratory flow. These four factors acted independently, and the effects were additive. It is suggested that environment in the early years of life can produce adverse changes which may exist throughout life and contribute to the development of chronic respiratory disease.