Analysis of new imidazoline derivative-induced increase in the maximum response to norepinephrine in the rat vas deferens

The effects of newly synthesized 5-imidazoline derivatives on the dose-response relationship to norepinephrine were investigated in the normal and denervated vasa deferentia of the rat. Three derivatives (K-3827, K-4011 and K-4300) exerted alpha-antagonistic action, the potency of which was similar to that of tolazoline. The pA2 values of these derivatives and currently known alpha-antagonists (tolazoline, phentolamine and prazosin, but not yohimbine) in the denervated tissue were slightly but significantly larger than those in the normal tissue. All imidazoline derivatives and alpha-antagonists produced an increase in the maximum response to norepinephrine in the normal vas deferens. In the denervated tissue, however, K-3827, K-4011 and alpha-antagonists caused only a rightward shift of the dose-response curve to norepinephrine, but not an increase in the maximum response, i.e., relatively pure alpha-antagonism. In contrast, the other 3 imidazoline derivatives, K-4299 and K-6342 which exhibited neither alpha-agonistic nor antagonistic action and K-4300, increased the maximum response to norepinephrine even after denervation. Their effects were nonspecific in that they also potentiated acetylcholine-induced contractions in both normal and denervated tissues. These 3 imidazoline derivatives antagonized the action of diltiazem. The effects of imidazoline derivatives and alpha-antagonists were discussed in relation to those of denervation, and the drug enhancement by 3 imidazoline derivatives was analyzed from the viewpoint of calcium movement.     

Influence of ouabain on the tracheal musculature of the dog

The effects of ouabain on the smooth muscles of the airway were investigated in anesthetized, paralyzed and artificially ventilated mongrel dogs. Ouabain (30 micrograms/kg, i.v.) caused a constriction of the tracheal smooth muscle which was followed by bradycardia. When ouabain was infused at a rate of 2 micrograms/kg/min (i.v.), the tracheal constriction was induced by a total dose of 45.0 +/- 5.5 micrograms/kg, while the bradycardia appeared with a total dose of 54.4 +/- 6.1 micrograms/kg. The ouabain-induced tracheal constriction was inhibited by bilateral vagotomy. The tracheal constriction induced by i.a. infusion of 10 microM ouabain into the bilateral cranial thyroid arteries was inhibited by bilateral vagotomy, but it was not completely blocked. With bilateral vagotomy, the tracheal constriction induced by i.a. infusion of ouabain was unaffected by 3 microM hexamethonium, but it was significantly inhibited by 1 microM atropine. These results suggest that ouabain may induce tracheal constriction by a neurogenic action in addition to its action via the augmentation of the vagal reflex, and the neurogenic action of ouabain may be related, in large part, to the release of acetylcholine from the presynapses of vagus nerves in dogs.     

Über die Kombination angeborener und erworbener Skeletterkrankungen

Ohne ZusammenfassungMit 16 Textfiguren und 3 Tafeln.     

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.     

Similarities between the relaxations induced by vasoactive intestinal peptide and by stimulation of the non-adrenergic non-cholinergic neurons in the rat stomach

Summary The characteristics of the non-adrenergic, noncholinergic inhibitory response of the rat stomach fundus to transmural nerve stimulation were compared with the relaxation induced by vasoactive intestinal polypeptide (VIP). Treatment with -chymotrypsin (5 U/ml) or VIP antiserum (1:200) significantly reduced the relaxation induced by transmural nerve stimulation at 30 Hz, indicating that the possible transmitter in the non-adrenergic, non-cholinergic nerves is a peptide and may be VIP or a closely related peptide. VIP was able to relax, fully and dose-dependently, the stomach fundus that had previously been constricted by treatment with 10^–6 M serotonin, and the IC₅₀ value for VIP was 2.4 × 10^–9 M. VIP elevated levels of cyclic AMP in a dose-dependent manner and the EC₅₀ value was 2.8 × 10^–9 M in the presence of 10^–6 M atropine and 10^–6 M guanethidine. The stomach fundus was relaxed by transmural nerve stimulation (30 Hz, 50 mA) and transmural nerve stimulation also caused production of cyclic AMP in the rat stomach in the presence of atropine and guanethidine. The basal level of cyclic AMP in the stomach was 8.7 ± 0.26 pmole/mg protein. When transmural nerve stimulation was applied for 5 min, the contraction of the stomach, induced by 10^–6 M serotonin, was inhibited by 54% in the presence of atropine and guanethidine and the level of cyclic AMP was increased to 13.0 ± 0.73 pmol/mg protein. Apamin inhibited the transmural nerve stimulation-induced relaxation and shifted the dose-response curve for VIP to the right. These results suggest that one of the putative neurotransmitter from non-adrenergic, non-cholinergic nerves in the rat stomach is VIP and that VIP-induced relaxation may be mediated by the production of cyclic AMP and by the opening of apamin-sensitive K⁺-channels.Send offprint requests to K. Kamata at the above address     

Radiotelemetry recording of electroencephalogram in piglets during rest

A wireless recording system was developed to study the electroencephalogram (EEG) in unrestrained, male Landrace piglets. Under general anesthesia, ball-tipped silver/silver chloride electrodes for EEG recording were implanted onto the dura matter of the parietal and frontal cortex of the piglets. A pair of miniature preamplifiers and transmitters was then mounted on the surface of the skull. To examine whether other bioelectrical activities interfere with the EEG measurements, an electrocardiogram (ECG) or electromyogram (EMG) of the neck was simultaneously recorded with the EEG. Next, wire electrodes for recording movement of the eyelid were implanted with EEG electrodes, and EEG and eyelid movements were simultaneously measured. Power spectral analysis using a Fast Fourier Transformation (FFT) algorithm indicates that EEG was successfully recorded in unrestrained piglets, at rest, during the daytime in the absence of interference from ECG, EMG or eyelid movements. These data indicate the feasibility of using our radiotelemetry system for measurement of EEG under these conditions.     

Ultrastructural and biochemical studies on the intestinal absorption of a medium-chain triglyceride (MCT), tricaprylin

The intestinal absorption of a medium-chain triglyceride (MCT) was studied by electron microscopy and biochemical analysis. In jejunal absorptive cells of rats fed tricaprylin, the smooth endoplasmic reticulum in the apical cytoplasm appeared to increase in number and contained one or two particles about 40–80 nm in diameter that were less electron dense and similar in size and profile to very low density lipoprotein. Similar particles were also observed packed in the dilated Golgi sacs and in the extended intercellular spaces. These particles were remarkably increased in number as compared with those in fasted rats. Biochemical analysis of lymph from the main intestinal lymph duct showed that caprylate was apparently demonstrated only in the lymph of rats given tricaprylin at the maximum rate 3h after oral administration. The study strongly suggests that medium-chain triglyceride is at least in part transported via lacteal, possibly in the form of very low density lipoprotein.     

Loss of the SEDL gene product (Sedlin) causes X‐linked spondyloepiphyseal dysplasia tarda: Identification of a molecular defect in a Japanese family

A 23‐year‐old man was diagnosed as having X‐linked spondyloepiphyseal dysplasia tarda (SEDT; MIM 313400) based on his disproportionately short trunk, short stature, characteristic radiological features of the spine (posterior hump, end plate sclerosis, and disc space narrowing) and the hips (short and thick femoral necks), and positive family history. This Japanese family was found to have an intragenic deletion flanking intron 2 and exon 3 of the SEDL gene that not only included the 5′ untranslated region but also the coding sequence for the first methionine through the 25th alanine. This mutation was present in the proband and his unaffected mother (a heterozygote), but not in an unaffected sister and an unaffected uncle. The nature of the mutation predicted that the SEDL protein (Sedlin) was not produced in the proband, indicating that loss of Sedlin caused SEDT. © 2001 Wiley‐Liss, Inc.