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Comparative studies of purinergic nerves.

Purinergic nerves supply the gastrointestinal tract of vertebrates, including fish, amphibians, reptiles and birds, as well as mammals. Their cell bodies are located in Auerbach's plexus and their axons extend in an anal direction before innervating mainly the circular muscle coat. In the stomach they are controlled by preganglionic cholinergic fibres of parasympathetic origin. They are involved in "receptive relaxation" of the stomach, "descending inhibition" in peristalsis and reflex relaxation of oesophageal and internal anal sphincters. The terminal varicosities of purinergic nerves are characterised by a predominance of "large opaque vesicles," which can be distinguished from the "large granular vesicles" found in small numbers in both adrenergic and cholinergic nerves. Stimulation of purinergic nerves with single pulses produces hyperpolarisations of up to 25 mV (inhibitory junction potentials) in smooth muscle cells. These potentials are unaffected by atropine, adrenergic neuron blocking agents or sympathetic denervation, but are abolished by tetrodotoxin. The "rebound contraction" which characteristically follows cessation of purinergic nerve stimulation is probably due to prostaglandin. Evidence that ATP is the transmitter released from purinergic nerves includes: (1) synthesis and storage of ATP in nerves; (2) release of ATP from the nerves when they are stimulated; (3) exogenously applied ATP mimicking the action of nerve-released transmitter, both producing a specific increase in K+ conductance; (4) the presence of Mg-activated ATPase, 5'-nucleotidase and adenosine deaminase, enzymes which inactivate ATP; (5) drugs (including quinidine, some 2-substituted imidazolines, 2-2'pyridylisatogen and dipyridamole) which produce similar blocking or potentiating effects on the response to exogenously applied ATP and nerve stimulation. Speculations are made about the evolution and development of the nervous system, including the possibility that purinergic nerves are a primitive nerve type.

Action Potentials

Effects of seasonal and social factors on testicular activity and hormone levels in domestic pigeons.

Testicular morphology and plasma concentrations of luteinizing hormone (LH), testosterone, progesterone, and estradiol-17beta were compared in paired (n = 8) and unpaired (n = 7) racing pigeons killed in December. The birds were housed mixed together under natural lighting conditions in two unheated lofts which contained no nesting facilities, in Kiel (54 degrees N), Germany. The paired birds had been paired for at least two months. Testicular weights and diameters of tubules were significantly higher (p less than 0.05) in paired (1.64 +/- 0.25 gm; 218 +/- 12 mum) than in unpaired birds (0.79 +/- 0.25 gm; 165 +/- 20 mum). The testes of paired birds were spermatogenetically more active than those of unpaired birds. Plasma concentrations of some hormones concerned with reproduction were, in paired and unpaired birds respectively: LH, 2.28 +/- 0.43 ng/ml and 0.98 +/- 0.36 ng/ml (significantly different, p less than 0.1); testosterone, 1.24 +/- 0.51 ng/ml and 0.59 +/- 0.12 ng/ml (not significantly different); progesterone, 0.58 +/- 0.08 ng/ml and 0.90 +/- 0.12 ng/ml (sifnificantly different, p less than 0.05); and estradiol-17beta, 16.3 +/- 0.95 pg/ml and 18.7 +/- 2.25 pg/ml (not significantly different). Thus, the stimulatory effects of a mate on gonadotropin secretion and gonadal activity which have often been reported for female ring doves and domestic pigeons are also demonstrable in males during the late fall. Seasonal testicular regression in the unpaired males at this time of year was not prevented by the presence of paired females.

Animals

Expression of an onco-developmental antegen among avian species.

Rabbit antisera directed against an onco-developmental antigen on chicken red blood cells have been serologically dissected through specific adsorptions. It is now possible to detect 13 antigenic determinants with the fractionated antisera. The onco-developmental antigen referred to as chicken fetal-leukemic antigen (CFA) is fetal-specific in the white Leghorn chicken, being present on the embryonic but not adult peripheral red blood cells of non-being present on the embryonic but not adult peripheral red blood cells of non-leukemic birds. However, one or more of the onco-developmental antigenic determinants have been detected on adult peripheral red blood cells of non-Gallus avian species, as well as on red blood cells from two adult chicken varieties. For phylogenetic purposes, red blood cells from avian species were characterized for their combinations of CFA determinants. Comparisons among species revealed specific patterns of antigenic expression within phylogenetic groups. Several CFA determinants were restricted in their occurrence to species within a single family, and one determinant was found in all cases where CFA was expressed. The distribution of CFA determinants was used to determine immunological distances among four Galliform species. These distances agreed with the immunological relationships established using different serological markers.

Animals

Forebrain projections of the pigeon olfactory bulb.

The olfactory system of the pigeon (Columba livia) was examined. Our electrophysiological and experimental neuroanatomical (Fink-Heimer technique) data showed that axons from the olfactory bulb terminated in both sides of the forebrain. The cortex prepiriformis (olfactory cortex), the hyperstriatum ventrale and the lobus parolfactorius comprised the uncrossed terminal field. The crossed field included the paleostriatum primitivum and the caudal portion of the lobus parolfactorius, areas which were reached through the anterior commissure. In this report the relationships between areas that receive olfactory information and the possible roles that olfaction plays in the birds' behavior are discussed.

Animals

The blood supply of muscle spindles in some mammals and the pigeon.

The blood supply of muscle spindles was studied in serial cross sections in macaque, cat, rabbit, guinea pig, mouse and pigeon muscles which had been incubated in a medium containing 3,3' diaminobenzidine. Lumina of blood vessels were recognized by the reaction product that was localized within erythrocytes. The outer capsule was well vascularized, but few or no capillaries were seen in the periaxial space. The inner spindle capsule, which closely invests the axial bundle, was rarely contacted by periaxial capillaries at the equator and juxtequator. Capillaries occurred more frequently adjacent to intrafusal fibers at the polar region and beyond the end of the outer capsule. Shorter diffusion distances and, usually, higher capillary densities were found at the polar region than at the spindle midsection. This suggests that transcapillary exchange at the polar segment is nearer to conditions prevalent in extrafusal muscle than elsewhere in the spindle, provided the inner and outer capsules are not less permeable at the poles than at the midsection. Differences in blood supply among mammalian species appear to be related to receptor size.

Animals

Vinblastine: influence on nerve conduction and synaptic transmission.

Vinblastine injected into the eyes of pigeons had a detrimental effect on the amplitude of the postsynaptic evoked potential in the optic tectum; impulse conduction of the optic nerve was not influenced. The depression of the postsynaptic evoked potential was dependent on the dosage. Only 20 and 100 mug vinblastine had an influence; no influence was observed with 10 mug vinblastine. The reversible depression was seen from the third day after injection to between the 21st and the 28th day after injection, and in that period it remained constant. The latency of the response was not influenced by vinblastine.

Animals

Requirement for guanosine triphosphate in the activation of adenylate cyclase by cholera toxin.

The activation of adenylate cyclase in lysed pigeon erythrocytes requires, among several cofactors, a nucleotide which may be ATP, GTP, or many other triphosphates. However, after removal of endogenous nucleotides by gel filtration or by adsorption onto charcoal the requirement can be met only by GTP, or an analog of GTP. The GTP is required during the activation of the cyclase by toxin even if GTP is also included during the subsequent adenylate cyclase assay, conducted without toxin. In the presence of GTP it is possible to assay for the cytosolic protein that is also required for the action of cholera toxin. By gel filtration, its apparent molecular weight is 15,000--20,000.

3',5'-Cyclic-AMP Phosphodiesterases

Cholera toxin-catalysed ADP-ribosylation of erythrocyte proteins: general properties.

Upon incubation of lysed pigeon erythrocytes with NAD, adenosine diphosphate-ribose (ADP-ribose) is incorporated into nuclear poly ADP-ribose and into an unidentified acid-insoluble product of the cytosol. The properties of these incorporations have been examined and a method developed for reducing their amount whilst retaining the sensitivity of the lysate to cholera toxin. This method has allowed the detection and description of a set of cholera toxin-specific ADP-ribose transfers to membrane-bound and soluble proteins under conditions that lead to adenylate cyclase activation.

Adenosine Diphosphate Sugars

Biological activity of a hypobetalipoproteinemic agent.

A new -ind of pharmacologic activity called hypobetalipoproteinemia is described. Iperationally the activity consists of a marked reduction of heparin precipitating lipoproteins (beta and/or pre-beta electrophoretic mobility) in hypercholesterolemic animals with a simultaneous decrease in the heparin precipitating lipoprotein: cholesterol ratio. As determined by ultracentrifugal fractionation of the lipoproteins from hypercholesterolemic rat serum, this activity consists of both a reduction in heparin precipitating lipoproteins and an increase high density lipoproteins that are not precipitated by heparin. Changes in composition were also induced in both lipoprotein fractions. The greatest changes were observed for free and esterified cholesterol, which were markedly reduced in the heparin precipitating lipoproteins and concomitantly increased in the high density lipoproteins. The hypobetalipoproteinemic agent exhibiting this activity is 1-[p-(1'-adamantyloxy) phenyl]-piperidine (U-41792). This agent is active in hypercholesterolemic rats, mice, quail, and pigeons.

Adamantane