I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

http://academic.oup.com/milmed/article-pdf/146/7/506/24126715/milmed-146-7-506.pdf

Goodman and Gilman's The Pharmacological Basis of Therapeutics

50 Years of Image Analysis

Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.

Cyclic Nucleotide-Gated Ion Channels

http://www.columbia.edu/cu/biology/courses/g4008x/readings03/genomics/Carlson%20Drosophila.pdf

A novel family of divergent seven-transmembrane proteins: candidate odorant receptors in Drosophila.

In the central nervous system (CNS) of both vertebrates and invertebrates, biogenic amines are important neuroactive molecules. Physiologically, they can act as neurotransmitters, neuromodulators, or neurohormones. Biogenic amines control and regulate various vital functions including circadian rhythms, endocrine secretion, cardiovascular control, emotions, as well as learning and memory. In insects, amines like dopamine, tyramine, octopamine, serotonin, and histamine exert their effects by binding to specific membrane proteins that primarily belong to the superfamily of G protein‐coupled receptors. Especially in Drosophila melanogaster and Apis mellifera considerable progress has been achieved during the last few years towards the understanding of the functional role of these receptors and their intracellular signaling systems. In this review, the present knowledge on the biochemical, molecular, and pharmacological properties of biogenic amine receptors from Drosophila and Apis will be summarized. Arch. Insect Biochem. Physiol. 48:13‐38, 2001. © 2001 Wiley-Liss, Inc.

/pdf/molecular-and-pharmacological-properties-of-insect-biogenic-2jy4p5scpz.pdf

Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera.

Cyclic nucleotide-gated (CNG) ion channels serve as downstream targets of signalling pathways in vertebrate photoreceptors and olfactory sensory neurons. Whether CNG channels subserve similar functions in invertebrate photoreception and olfaction is unknown. We have cloned genomic DNA and cDNA encoding a cGMP-gated channel from Drosophila. The gene contains at least seven exons. Heterologous expression of cloned cDNA in both Xenopus oocytes and HEK 293 cells gives rise to functional ion channels. The Drosophila CNG channel is approximately 50-fold more sensitive to cGMP than to cAMP. The voltage dependence of blockage by divalent cations is different compared with the CNG channel of rod photoreceptors, and the Ca2+ permeability is much larger. The channel mRNA is expressed in antennae and the visual system of Drosophila. It is proposed that CNG channels are involved in transduction cascades of both invertebrate photoreceptors and olfactory sensillae.

/pdf/primary-structure-and-functional-expression-of-a-drosophila-zlyjt5d0xr.pdf

Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae.

Biogenic amines and their receptors regulate and modulate many physiological and behavioural processes in animals. In vertebrates, octopamine is only found in trace amounts and its function as a true neurotransmitter is unclear. In protostomes, however, octopamine can act as neurotransmitter, neuromodulator and neurohormone. In the honeybee, octopamine acts as a neuromodulator and is involved in learning and memory formation. The identification of potential octopamine receptors is decisive for an understanding of the cellular pathways involved in mediating the effects of octopamine. Here we report the cloning and functional characterization of the first octopamine receptor from the honeybee, Apis mellifera. The gene was isolated from a brain-specific cDNA library. It encodes a protein most closely related to octopamine receptors from Drosophila melanogaster and Lymnea stagnalis. Signalling properties of the cloned receptor were studied in transiently transfected human embryonic kidney (HEK) 293 cells. Nanomolar to micromolar concentrations of octopamine induced oscillatory increases in the intracellular Ca2+ concentration. In contrast to octopamine, tyramine only elicited Ca2+ responses at micromolar concentrations. The gene is abundantly expressed in many somata of the honeybee brain, suggesting that this octopamine receptor is involved in the processing of sensory inputs, antennal motor outputs and higher-order brain functions.

Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain.

In invertebrates, the biogenic-amine octopamine is an important physiological regulator. It controls and modulates neuronal development, circadian rhythm, locomotion, ‘fight or flight’ responses, as well as learning and memory. Octopamine mediates its effects by activation of different GTP-binding protein (G protein)-coupled receptor types, which induce either cAMP production or Ca2+ release. Here we describe the functional characterization of two genes from Drosophila melanogaster that encode three octopamine receptors. The first gene (Dmoa1) codes for two polypeptides that are generated by alternative splicing. When heterologously expressed, both receptors cause oscillatory increases of the intracellular Ca2+ concentration in response to applying nanomolar concentrations of octopamine. The second gene (Dmoa2) codes for a receptor that specifically activates adenylate cyclase and causes a rise of intracellular cAMP with an EC50 of ∼3 × 10−8 m octopamine. Tyramine, the precursor of octopamine biosynthesis, activates all three receptors at ≥ 100-fold higher concentrations, whereas dopamine and serotonin are non-effective. Developmental expression of Dmoa genes was assessed by RT–PCR. Overlapping but not identical expression patterns were observed for the individual transcripts. The genes characterized in this report encode unique receptors that display signature properties of native octopamine receptors.

http://www.molekulare-physiologie.de/publication/pdf/octo.pdf

A family of octapamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster

Biogenic amine receptors are involved in the regulation and modulation of various physiological and behavioral processes in both vertebrates and invertebrates. We have cloned a member of this gene family from the CNS of the honeybee, Apis mellifera. The deduced amino acid sequence is homologous to tyramine receptors cloned from Locusta migratoria and Drosophila melanogaster as well as to an octopamine receptor cloned from Heliothis virescens. Functional properties of the honeybee receptor were studied in stably transfected human embryonic kidney 293 cells. Tyramine reduced forskolin-induced cyclic AMP production in a dose-dependent manner with an EC50 of approximately 130 nM. A similar effect of tyramine was observed in membrane homogenates of honeybee brains. Octopamine also reduced cyclic AMP production in the transfected cell line but was both less potent (EC50 of approximately 3 microM) and less efficacious than tyramine. Receptor-encoding mRNA has a wide-spread distribution in the brain and subesophageal ganglion of the honeybee, suggesting that this tyramine receptor is involved in sensory signal processing as well as in higher-order brain functions.

Arnd Baumann

Papers

Molecular and pharmacological properties of insect biogenic amine receptors: lessons from Drosophila melanogaster and Apis mellifera.

Primary structure and functional expression of a Drosophila cyclic nucleotide-gated channel present in eyes and antennae.

Molecular and functional characterization of an octopamine receptor from honeybee (Apis mellifera) brain.

A family of octapamine receptors that specifically induce cyclic AMP production or Ca2+ release in Drosophila melanogaster

Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor.