Quaternary narcotic antagonists' relative ability to prevent antinociception and gastrointestinal transit inhibition in morphine-treated rats as an index of peripheral selectivity

Single doses of naloxone (0.025 to 0.5 mg/kg) or of one of four quaternary narcotic antagonists (i.e. nalorphine allobromide, nalorphine methobromide, naloxone methobromide or naltrexone methobromide, 1 to 60 mg/kg) were given s.c. to rats before morphine, 5 mg/kg i.v. In the absence of antagonists morphine reduced G.I. transit of a charcoal meal to about 15% of drug-free controls and consistently delayed nociceptive reactions (55°C hot plate) in all animals. Doses of antagonists slightly reducing morphine antinociception (centrally effective = A) and restoring G.I. transit to about 50% of drug-free rats (peripherally effective = B) were estimated. The A:B ratio, indicating peripheral selectivity, was at least 8 for any of the quaternary antagonists given 10 min before morphine, but prolonging this interval may have resulted in a lower figure (i.e. less peripheral selectivity) because of reduced A and increased B. This was definitely so for naltrexone methobromide (A:B, > 60 at 10 min, about 1 at 80 min) and was not apparent for nalorphine methobromide according to available data, which for nalorphine allobromide and to a lesser extent for naloxone methobromide showed only an increase in B at intervals longer than 10 min. Both morphine-induced antinociception and inhibition of G.I. transit were reduced by naloxone at the lower doses tested and were fully prevented at the higher. These findings indicate that, unlike naloxone, the investigated quaternary narcotic antagonists are interesting prototype drugs for selective blockade of opiate receptors outside the CNS, although certain critical aspects, possibly biological N-dealkylation to the corresponding tertiary antagonists, condition peripheral selectivity.     

Phospholipid composition and external labeling of aminophospholipids of human En(a−) erythrocyte membranes which lack the major sialoglycoprotein (glycophorin a)

Erythrocytes of the rare human blood group En(a?) lack the major sialoglycoprotein, glycophorin A, and the cell population heterozygous for the En(a) antigen contain half the normal amount of glycophorin A. With such cells we have studied whether glycophorin A influences the phospholipid composition and the availability of aminophospholipids to external labeling reagents. We here demonstrate that the amounts of all phospholipids are closely similar in normal and variant membranes. However, using the amino-reactive reagent trinitrobenzenesulfonate, we show that phosphatidylethanolamine is more easily labeled in intact En(a?) cells as compared to normal cells, whereas phosphatidylethanolamine shows an intermediate labeling in En(a) heterozygous cells.     

Aggressive behaviour of female prairie deer mice in laboratory populations

Prairie deer mice (Peromyscus maniculatus bairdii), living in asymptotic laboratory populations established two years earlier, were observed for agonistic responses to conspecific intruders. In the first experiment, intruders of six age-sex classes were placed into 10 of the populations for 10 min. The sex of the intruder did not influence the behaviour of the residents, but juveniles elicited more aggression than did adults. A second experiment revealed that female residents were responsible for almost all of the attacks upon juveniles. Experiment 3, in which the responses of pairs of deer mice to juvenile intruders were recorded, demonstrated that the aggressiveness of a female was enhanced by the presence of a male. In the final experiment, females were observed to be highly aggressive during the first few days after giving birth. The aggressive behaviour of the female deer mouse may have greater significance for population dynamics than that of the male.     

Stimulation of gastrin secretion from the perfused rat stomach by somatostatin antiserum

The effect of a high capacity somatostatin antiserum on antral gastrin secretion was examined in an isolated vascularly perfused rat stomach preparation. Infusion of somatostatin antiserum diluted 1:1 and 1:9 with Krebs buffer solution produced significant increases in gastrin secretion throughout the period of infusion. Neither infusion of somatostatin antiserum diluted 1:99 nor infusion of control rabbit serum had any effect on gastrin secretion. The data indicate that antral somatostatin excercises a continous restraint on gastrin secretion in the basal state.     

Integration of foreign genome fragments into cells transformed or cotransformed with fragmented adenoviral DNA

The integration of DNA of highly oncogenic simian adenovirus type 7 (SA7) and non-oncogenic human adenovirus type 6 (Ad6) into the genome of newborn rat kidney cells transformed by fragmented DNA preparations was studied using reassociation kinetics and spot hybridization. Transforming DNA was fragmented with the specific endonuclease SalI (SA7) and BglII (Ad6). In contrast to the cell transformation by intact viral DNA, transformation by fragmented DNA resulted in integration into the cellular genome of not only the lefthand fragment with the oncogene but also of other regions of the viral genome. Additionally integrated fragments were stable and preserved during numerous passages of cells lines, although they were no expressed, at least in the case of the Ad6-transformed cell line. The integration of the fragments of SA7 DNA was accompanied by loss of 25-50% of the mass of each fragment. Adding the linear form of the pBR322 plasmid to the preparation of transforming Ad6 DNA also contributed to its cointegration into the genome of the transformed cell. This technique of cell cotransformation with any foreign DNAs together with the viral oncogens may be used as an equivalent of an integration vector for eukaryotic cells.     

Recombination between satellite phage P4 and its helper P2. I. In vivo and in vitro construction of P4: :P2 hybrid satellite phage

P4::P2 hybrid satellite phages which carry a portion (including the P2 head gene Q and the cohesive end) of the left end of the P2 chromosome linked to the essential part of the P4 chromosome have been isolated by in vivo as well as in vitro recombination. These hybrids express gene Q and grow in the presence of a P2 helper even if defective in gene Q.     

Nutrient inflows into apple roots. I. 32P-orthophosphate uptake from solution by M.9 rootstocks and Worcester Pearmain seedlings

Abstract. The rates of uptake of ³²P-labelled orthophosphate by whole root systems of young apple trees (M.9 rootslocks and Worcester Pearmain seedlings) were measured in solution culture. Using a solution depletion technique, the ³²P-phosphate uptake rates per unit length, surface area or fresh weight of roots were determined as a function of ³²P-phosphate concentration in solution at the root surface over the range 0.25–10 mmol m⁻³. The effect of P concentration within various plant parts on the relation between uptake rate and external P concentration was studied using plants differing in internal P levels.
The apparent minimutn P concentration below which P uptake ceased was of the order of 0.25–0.50 mmol m⁻³. Fluxes, inflows and unit absorption rates increased approximately proportionately with solution concentration up to 10mmolm⁻³. Except perhaps in the case of the low-P M.9 plant, there was no evidence of a diminishing returns type of relationship over the range of solution concentrations examined. The threshold P concentration in solution above which uptake rates cease to increase thus appears to be higher for apples than for other species.
At any given P concentration, fluxes, inflows and unit absorption rates were higher for M.9 than for Worcester and for low-P plants than for high-P plants. The difference between plants of different P status was more marked for M.9 and seems to be more closely related to shoot P levels than to root P.     

Ionomycin-mediated calcium transport in rigid and fluid liposomes

The antibiotic ionophore ionomycin translocates Ca from an aqueous medium into or across an organic immiscible phase. At pH 8.0, ionomycin translocates less Ca than A23187, the effects of these ionophores being additive to one another. The capacity of ionomycin to translocate Ca across the organic phase is dramatically decreased when the pH of the aqueous media is reduced from 8.0 to 7.5 or lower values. Ionomycin also mediates Ca exchange-diffusion in liposomes, the magnitude of such a process being greater in fluid than in rigid liposomes. At a physiological pH (7.4), ionomycin is unexpectedly as potent as A23187 in mediating Ca transport in fluid liposomes. These findings suggest that the capacity of ionophores to translocate Ca across model membranes depends on both the transverse and lateral mobility of the ionophoretic molecules. The relative importance of the latter phenomenon itself largely depends on the stoichiometry of the Ca-ionophore complex.     

Material transport within specialised ciliary shafts on Rhabdopleura zooids

Summary The surface of the Rhabdopleura zooid is ciliated. The cilia of the cephalic shield and tentacles have paddle-like swellings of the shaft. These swellings are usually about 0.6–1 m in diameter and most frequently found in the distal 1–2 m of the ciliary shaft. Others are found in other positions along the length of the cilium and it is suggested that at least some of these swellings represent material transport within the cilium.Paddle shaped cilia are probably more efficient than normal cilia in moving water and food particles. If these cilia are involved in the building of the tubular coenecium then their distribution suggests that the tentacles as well as the cephalic shield are actively involved in tube building.I should like to thank the director and staff of the Marine Biological Laboratory, Plymouth, for collecting the material and the generous loan of facilities during the preparation of the material. Mr. R. Moss provided skillful technical and photographic assistance