Serotonin and thermoregulation: old and new views

An overview is presented of the evidence favouring a pivotal role for serotoninergic neurons in the diencephalon's control system for body temperature. 1. Morphological investigations of the anterior hypothalamus reveal that 5-HT injected locally into this thermosensitive zone evokes a hyperthermia in virtually all species. Pharmacological blocking agents of serotoninergic receptors antagonize the 5-HT-induced rise in an animal's temperature. 2. Further, the destruction of serotoninergic neurons in the anterior hypothalamic pre-optic area of a rat or monkey severely impairs the heat production responses during cold stress. 3. In addition, the release of 5-HT from anterior hypothalamic tissue is enhanced significantly when the animal is exposed to a cold environmental temperature, and subsequently shivers, vasoconstricts and conserves heat. 4. New observations are described which show that 5-HT may elicit a fall in temperature as a result of the: (1) overloading of 5-HT receptor sites in the anterior hypothalamus; and/or (2) occupation by 5-HT of either noradrenergic or dopaminergic receptors, or both classes of catecholamine receptors which are believed to mediate the hypothalamic pathways for heat loss. 5. Finally, new data also implicate neuronal 5-HT, again only within the anterior hypothalamic pre-optic area, in the cellular mechanism which triggers a fever in response to a bacterial challenge. Thus, the serotoninergic neurons underlying the rostral hypothalamic temperature controller are responsible not only for the defense of an animal's body temperature during exposure to cold, but also for initiating the shift in the temperature "set-point" during a febrile episode.     

Comparative studies of the mosquito-larval toxin of Bacillus sphaericus SSII-1 and 1593

Two strains of Bacillus sphaericus. SSII-1 and 1593, were bioassayed for toxic activity against second-instar larvae of the mosquito Culex pipiens quinquefasciatus. It was found that strain 1593 developed a level of toxicity 3000 times that of strain SSII-1. Although the toxic activity of B. sphaericus SSII-1 was relatively unchanged throughout growth, an increase in activity of strain 1593 occurred as the bacteria began to sporulate. Strain differences were examined by (i) growth cycle experiments, (ii) bioassays of the toxicity of oligosporogenous mutants, and (iii) manganese limitation experiments. The toxin of strain 1593 was shown to be more stable than that of strain SSII-1. Unlike the spores of strain SSII-1, the spores of B. sphaericus 1593 were found to be highly toxic. Thin sections of SSII-1 or 1593 cells did not reveal the presence of any inclusion body that might be related to toxicity.     

Morphology of the granular secretory glands in skin of poison-dart frogs (Dendrobatidae)

The granular glands of nine species of dendrobatid frogs were examined using light and electron microscopy. The glands are surrounded by a discontinuous layer of smooth muscle cells. Within the glands proper the secretory cells form a true syncytium. Multiple flattened nuclei lie at the periphery of the gland. The peripheral cytoplasm also contains mitochondria, rough surfaced endoplasmic reticulum, the Golgi apparatus, and an abundance of smooth endoplasmic reticulum. Centrally, most of the gland is filled with membrane-bound granules surrounded by amorphous cytoplasm. Few other organelles are found in this region. Early in the secretory cycle, the central part of the gland is filled with flocculent material which appears to be progressively partitioned off by membranes to form the droplet anlage. As granules form, the structure of the contents becomes progressively more vesicular. Dense vesicles, which bud off from the Golgi apparatus, fuse with the granular membrane during the development of granules, and might contain enzymes involved in toxin synthesis. The granules at this point resemble multivesicular bodies. Their structure is similar in all species of dendrobatid frogs even though the different frogs secrete substances of different chemical structure and toxicity.     

Binding of adenosine 3',5'-monophosphate dependent protein kinase regulatory subunit to immobilized cyclic nucleotide derivatives.

Several cyclic nucleotide derivatives with aminoalkyl side chains attached to the purine ring were synthesized and their interactions with adenosine 3',5'-monophosphate (cAMP) dependent protein kinase were studied before and after immobilization to CNBr-activated Sepharose 4B. The soluble N6-substituted derivatives were as effective as cAMP itself in activating protein kinase and were more effective than 8-substituted cAMP derivatives, whereas the 2-substituted cAMP derivatives and the cGMP derivatives were the least effective. All of the synthetic derivatives tested were poor substrates for beef heart phosphodiesterase being hydrolyzed at rates less than 2% for that of cAMP itself. Utilizing methodology developed to evaluate the affinity of protein kinase for immogilized cyclic nucleotides it was found that all of the immobilized cyclic nucleotides interacted with protein kinase in a biospecific manner as judged by the following criteria: (1) the immobilized cyclic nucleotides competed with cAMP for the binding sites on protein kinase; (2) the analogous spacer-arm did not compete; and (3) the effects of enzyme concentration, MgATP, and cleavage of the cyclic phosphate ring on the interactions of protein kinase with the immobilized cyclic nucleotides were the same as previously shown for free cAMP. In addition, the immobilized ligands were bound with the same order of effectiveness as the analogous soluble ligand. The observed Ka for the activation of 0.005 muM protein kinase by N6-H2N(CH2)2-cAMP was increased from 0.23 to 3 muM by the process of immobilization. This increase was unaffected by the coupling density and spacer-arm length. The observed Kb for 0.10 muM protein kinase binding to immobilized N6-H2N(CH2)2-cAMP was increased as the molecular sieving exclusion limit of the matrix used was decreased indicating that at least part of this decrease in apparent affinity upon immobilization is due to exclusion of the enzyme from a portion of the matrix and therefore of the immobilized ligand molecules.     

Nonautotrophic Thiobacillus in Acid Mine Water

Nonautotrophic thiobacilli were isolated from the acidic water of a coal mine. Based on their mixotrophic physiology, the isolates are regarded as strains of Thiobacillus perometabolis.     

A second specific endonuclease from Haemophilus aegyptius.

A second restriction-like endonuclease has been partially purified from Haemophilus aegyptius. This enzyme cleaves bacteriophage λ DNA and adenovirus 2 DNA at many sites, but cleaves simian virus 40 DNA at only one site.