Neuronal 5-hydroxytryptamine receptors outside the central nervous system

5-HT receptors are present on many types of neurone in the peripheral nervous system (PNS), e.g. sympathetic, parasympathetic, enteric and sensory cells, and mediate complex effects. These include depolarization, cell discharge and facilitation or depression of transmission. If 5-HT receptors can be classified according to the membrane mechanism associated with them, following the system adopted for mollusc neurones, such a classification would have to take into account two kinds of presynaptic and at least four kinds of postsynaptic action. Recent work suggests that a small number of analogues of 5-HT (tryptamine, 5-MOT, LSD) and antagonists (cocaine, methysergide, quipazine) may be useful in differentiating the various kinds of 5-HT receptor in the PNS. It is suggested that no single feature should be relied upon to characterize the receptors; classification might be based on consideration of function, evidence of tachyphylaxis, sensitivity to methysergide, cocaine, etc. On this basis, it is tentatively concluded that there are two kinds of 5-HT receptor mediating excitation in the PNS, neither of which can sensibly be termed an ‘M’ receptor. An interim form of terminology is proposed which makes use of an acronym of the distinctive features. A receptor mediating (E)xcitation, which shows (T)achyphylaxis, is (M)ethysergide (I)nsensitive but is blocked by (C)ocaine might be designated a 5-HT_ETMIC receptor, while a second which differs because it is insensitive to cocaine but activated by (F)ive-methoxytryptamine might be designated a 5-HT_ETMIF receptor. Amongst receptors mediating (I)nhibition, the best characterized is one mediating decreased transmitter release and activated by (L)SD. The term 5-HT_IL receptor is proposed. A second, post-synaptic inhibitory receptor is likely, but has not been adequately characterized at present.     

Immunological and receptor-binding properties of fragments resulting from cyanogen bromide cleavage of bovine growth hormone

Fragments obtained from bovine growth hormone (somatotropin) by cyanogen bromide cleavage were isolated and identified. Their activities were investigated in a radioimmunoassay for bovine growth hormone and in a radioreceptor assay for growth hormone which uses membrane-associated receptors from the liver of a pregnant rabbit. At least one antigenic determinant and the receptor-binding site could be located in the sequence comprising residues 1-124/6-124 plus 150–179 (disulfide-linked), although they appeared not to be identical. An apparent increase in affinity compared with unfractionated cyanogen bromide-cleaved hormone was observed in both assays for the fraction containing these fragments. Neither intactness of methionyl residues nor that of the hormone appeared to be absolutely required for antibody-binding and receptor-binding activity (although other antigenic determinants may have been lost as a result of cleavage). However, the activities of the disulfide-linked fragment were low, indicating that conformational or other changes had modified the antibody-binding and receptor-binding sites.     

The extents of formation of cobalt(II)-radical intermediates in the reactions with different substrates catalysed by the adenosylcobalamin-dependent enzyme ethanolamine ammonia-lyase

1. The reactions of the adenosylcobalamin-dependent enzyme, ethanolamine ammonia-lyase, with the 'good' and 'relatively poor' substrates 2-aminoethanol and (S)-2-aminopropanol respectively, under conditions of saturation with substrate were investigated by rapid freezing in conjunction with electron paramagnetic resonance (e.p.r.) spectroscopy and by stopped-flow spectrophotometry. 2. In disagreement with earlier reports [Babior et al. (1972) J. Biol. Chem. 247, 4389-4392], it was found that the reaction of 2-aminoethanol gave an e.p.r. signal observed in rapid freezing experiments characteristic of a coupled Co(II)-free radical system. This signal was similar to, though not identical with, that obtained with (S)-2-aminopropanol. The steady-state level of the signal with 2-aminoethanol as substrate was 0.56 of that attained with (S)-2-aminopropanol. 3. The results of these e.p.r. experiments were shown to be consistent with stopped-flow data obtained under closely similar reaction conditions, the latter indicating a corresponding ratio of 0.64. The results also are consistent with those of a rapid wavelength scanning, stopped-flow spectrophotometric study [Hollaway et al. (1978) Eur. J. Biochem. 82, 143-154].     

Concentration of poliovirus from tap water onto membrane filters with aluminum chloride at ambient pH levels.

A method is described for the concentration of an enterovirus from large volumes of tap water by addition of small amounts of aluminum chloride to enhance virus removal by membrane filters. Tap water treated with 2 X 10(-5) M aluminum chloride showed a slight decrease in pH (less than 0.5), a slight increase in turbidity, and enhanced removal of poliovirus by membrane filters. Virus was quantitatively recovered by treating the filters with a basic buffer, and this eluate was reconcentrated to a small volume by adsorption to aluminum hydroxide flocs. Using these procedures, virus from 1,000 liters of water was reduced to a final eluate of 20 to 80 ml with a mean recovery of 70%.     

The molecular evolution of pituitary growth hormone prolactin and placental lactogen: A protein family showing variable rates of evolution

Summary Pituitary growth hormone and prolactin, together with the homologous placental hormones, comprise a family of related protein hormones. Complete or partial amino acid sequences of seven mammalian growth hormones, six mammalian prolactins and one placental lactogen are available, and have been compared. A phylogenetic tree has been constructed which describes the relationships within the family. At least two gene duplications have occurred during the evolution of these proteins. Rates of evolution in the family have been quite variable, the overall rate of evolution having been apparently fairly slow, but having increased markedly on several occasions, most notably in the evolution of human (and, on the basis of immunological relationships, probably other primate) growth hormones and rat (and possibly other rodent) prolactins.     

The action of isoprenaline on the electrophysiological properties of hypertrophied left ventricular myocytes.

The electrophysiological effects of the beta-agonist, isoprenaline, on hypertrophied left ventricular myocardium were measured to understand better the arrhythmic effects of beta-stimulation on the hypertrophied heart. Left ventricular hypertrophy was induced in guinea-pigs by constriction of the thoracic aorta. An age-matched sham-operated group served as controls. Isolated myocytes were held under voltage- and current clamp and the effect of isoprenaline on the L-type Ca2+ current, I(Ca), a Cl- current, I(Cl), and action potential morphology were measured. Cardiac growth was mirrored by cellular hypertrophy. I(Ca) and I(Cl) current density were reduced as myocyte hypertrophy progressed. The augmentation of I(Ca) and I(Cl) by isoprenaline was also reduced in hypertrophy, but no other characteristics of the two currents, or the dose-dependency of the action of isoprenaline were a function of cardiac growth. Isoprenaline prolonged the action potential, but to a smaller extent in hypertrophied myocytes. This difference in action potential prolongation was abolished by glibenclamide. The changes to I(Ca) and I(Cl) in hypertrophy would not tend to increase triggered activity in this situation. Under maximum inotropic stimulation hypertrophied myocytes show action potential changes which are consistent with intracellular ATP depletion, and which could enhance the likelihood of re-entrant circuits. A simple diffusion model for oxygen is constructed to demonstrate the possibility of cellular hypoxia in hypertrophied myocytes.     

Structural and possible thermoregulatory differences in the ears of grey kangaroos

1. 1. Western Grey Kangaroos generally inhabit more arid and hotter regions than Eastern Greys.

2. 2. Ears from Western Greys are significantly thinner, less furred and have smaller, thinner hairs than those from Eastern Grays.

3. 3. Ears may act as better heat dissipators in the Western Greys than in the Eastern Greys.