Sympathetic vasodilation in the submaxillary gland and its enhancement after chronic parasympathetic denervation

Zusammenfassung Die «Nacherweiterung» der Gefässe, welche auf Reizung des sympathischen Nervs der Submaxillaris-Drüse in der Katze folgt, wird nicht durch Kallikrein oder Kinin ausgelöst, da sie nicht durch den hochwirksamen synthetischen Bradykinin-potenzierenden Faktors (BPF) beeinflusst wird. Eine neue Beobachtung zeigte, dass diese sympathische Gefässerweiterung bedeutend verstärkt wird, nachdem der parasympathische Nerv durchschnitten wurde und degeneriert ist.

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This work was supported by grants from the Medical Research Council of Canada and the Alberta Heart Foundation.     

Human platelet 5-hydroxytryptamine receptors: binding of [3H]-lysergic acid diethylamide (LSD). Effects of chronic neuroleptic and antidepressant drug administration

Chronic treatment with phenothiazines and thioxanthenes has been found to enhance 5-HT-induced aggregation of human platelets. A method has been developed to study 5-HT2 receptor binding sites on platelets utilising [3H]-LSD and more recently 125I/LSD. Results are presented which suggest that the LSD binding site is indeed the 5-HT2 binding site and that the LSD binding characterises the specific receptor responsible for 5-HT-induced shape change and aggregation. In a group of patients receiving phenothiazines or thioxanthenes, the Bmax of LSD binding was increased. The mean binding affinity was decreased possibly due to a persistence of neuroleptic in the platelet membrane preparation. Analysis showed that this was not the reason why the mean binding capacity was increased. The results show that chronic phenothiazine and thioxanthene delta treatment 'up-regulates' platelet 5-HT2 binding sites and that this may be accompanied by increased sensitivity to platelet aggregation by 5-HT. In normal subjects desipramine treatment increased the Bmax of platelet LSD binding and this was accompanied by an increased prolactin response to tryptophan which is thought to be mediated by central 5-HT function.     

Gastric secretion during anaesthesia and its inhibition by metiamide and other drugs.

The histamine H2-receptor antagonist, metiamide, inhibits the acid gastric secretion produced by chloralose-urethane anaesthesia in dogs carrying gastric cannulae chronically. This secretion is also prevented by atropine and hexamethonium. "Spontaneous" gastric secretion of vagal origin in conscious dogs is also blocked by metiamide.     

Effect of nerve stimulation,denervation, and duct ligation,on kallikrein content and duct cell granules of the cat's submandibular gland

Summary Various procedures which reduce or deplete the kallikrein content of the cat's submandibular gland correspondingly reduce the number of apical granules in the striated duct cells. The kallikrein content is greatly reduced after chronic parasympathetic but not after sympathetic nerve section which suggests that the parasympathetic innervation is required for synthesis or storage of this enzyme.We wish to acknowledge the valuable assistance of Dr T. Nihei and Mr. J. Wimal in some of the enzyme measurements.This work was supported by grants from the Medical Research Council of Canada and the Alberta Heart Foundation.     

The effect of a bradykinin antagonist on vasodilator responses with particular reference to the submandibular gland of the cat

A bradykinin analogue, D-Arg[Hyp3, Thi5,8, D-Phe7]-Bk, antagonized the vasodilator effect of bradykinin injected close-arterially in the submandibular salivary gland of the cat, without affecting that due to acetylcholine or nerve stimulation. The same analogue also antagonized the hypotensive response to bradykinin injected intravenously in cats and rabbits. We conclude that functional hyperaemia in the submandibular gland of the cat is not due to the release of bradykinin by salivary kallikrein.     

ISPD loss-of-function mutations disrupt dystroglycan O-mannosylation and cause Walker-Warburg syndrome

Walker-Warburg syndrome (WWS) is clinically defined as congenital muscular dystrophy that is accompanied by a variety of brain and eye malformations. It represents the most severe clinical phenotype in a spectrum of diseases associated with abnormal post-translational processing of a-dystroglycan that share a defect in laminin-binding glycan synthesis1. Although mutations in six genes have been identified as causes of WWS, only half of all individuals with the disease can currently be diagnosed on this basis2. A cell fusion complementation assay in fibroblasts from undiagnosed individuals with WWS was used to identify five new complementation groups. Further evaluation of one group by linkage analysis and targeted sequencing identified recessive mutations in the ISPD gene (encoding isoprenoid synthase domain containing). The pathogenicity of the identified ISPD mutations was shown by complementation of fibroblasts with wild-type ISPD. Finally, we show that recessive mutations in ISPD abolish the initial step in laminin-binding glycan synthesis by disrupting dystroglycan O-mannosylation. This establishes a new mechanism for WWS pathophysiology.     

Analysis of vasodilatation in the submaxillary gland using potentiators of acetylcholine and kinins

Zusammenfassung Nachweis, dass bei Reizung des N. chorda lingualis der Katze ein Blutdruckeffekt ausbleibt, wenn ein Bradykinin potenzierender Faktor (Präparat BPF) zuvor gegeben wurde.

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Acknowledgments. We are greatly indepted to Dr.J. Stewart of the University of Colorado and to Dr.L. Greene of Brookhaven National Laboratories, New York, for kind gifts of synthetic bradykinin potentiators.

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This work was supported by grants from the Medical Research Council of Canada and the Alberta Heart Foundation.