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Biomedical subjects

C Brink

Publications and source records attributed to C Brink.

95 records · Page 6Linked to original sources
PubMedDate not supplied

Cholinergic control of human and animal pulmonary vascular tone.

The regulation of pulmonary vascular tone by acetylcholine (ACh) involves the activation of different subtypes of muscarinic receptors as well as the cholinesterase activities which are responsible for ACh degradation. Most of the studies on the cholinergic control of the pulmonary vascular tone have been performed in vessels derived from animals. The ability of ACh to induce pulmonary vasoconstriction is species dependent. In vessels derived from sheep lung, ACh induced contractions in veins but not in arteries whereas in human pulmonary vessels the reverse was observed. The subtype(s) of the muscarinic receptors involved in the pulmonary vasoconstrictions is also dependent on the species which are studied. M1 receptors are implicated in the rabbit pulmonary vasoconstrictions, M3 in humans, whereas M1 and M2 receptors are involved in the dog. The cholinesterases are implicated in the vasoconstriction produced by ACh in human and rabbit pulmonary arteries. However, in these studies while acetylcholinesterase (EC 3.1.1.7) and butyrylcholinesterase (EC 3.1.1.8) activities were detected in human vessels only acetylcholinesterase activity was found in rabbit vessels. The endothelium-dependent relaxation induced by ACh has been reported in isolated pulmonary vessels from different animals including man. However, the muscarinic receptors involved in the ACh-induced vasodilatation of rat and rabbit pulmonary artery are of the M3 subtype while those characterized in the human pulmonary artery are of the M3 and M1 subtypes. Together these results concerning the cholinergic control of the pulmonary vascular tone indicate that extrapolation of the data obtained in animal models to human vessels requires some caution. In addition, there is considerable evidence to demonstrate that ageing may modify cholinergic responses. However, little information is available concerning the pulmonary vascular bed during ageing.

Acetylcholine↗
PubMedDate not supplied

Development of a functional human bronchial model of mucin secretion.

In an attempt to study the functional aspects of respiratory mucin secretion and the effects of mediators of inflammation on the release of M1/MUC5AC mucins in airways diseases, an ex vivo human bronchial model of mucin secretion was developed. Anti-M1 mucin monoclonal antibodies raised against the peptidic core of ovarian cyst M1 mucins were used. PAS and Alcian blue stainings of sections of bronchial rings revealed the presence of mucins in epithelial goblet cells as well as in glandular mucous cells. Immunohistochemical labelling of these sections with anti-M1 monoclonal antibodies revealed a preferential localization of M1/MUC5AC mucins in epithelial goblet cells. Functional studies were performed on this bronchial model using various secretagogues (methacholine, leukotrienes D4 and anti-human immunoglobulin E antibodies). No statistical difference of M1/MUC5AC mucin secretion was observed after a one-hour stimulation of bronchial rings with these agents. The development of an ex vivo functional human bronchial model of mucin secretion and the use of specific anti-M1 antibodies are essential tools in studying the regulation of the M1/MUC5AC mucin release from human airways.

Antibodies, Monoclonal↗
PubMedDate not supplied

The muscarinic receptor subtypes in human blood vessels.

Acetylcholine (ACh) may induce the relaxation and the contraction of human blood vessels. These effects involve the activation of muscarinic receptors located on endothelial or smooth muscle cells. In humans and animals, five subtypes of muscarinic receptors (M1-M5) have been identified. In the particular case of human blood vessels, the M3 subtype seems to be prevalent on endothelial cells as well as on smooth muscle cells. However, the M1 subtype may be specific for the pulmonary vascular endothelium. In contrast, the M4 subtype has not been described in human vessels. These conclusions are, however, based on a limited number of studies and further work is needed in this area of research. Although muscarinic receptors may not be the only receptors involved in hypertension, the development of specific agonists for M1 receptors may be useful to counteract any elevation of blood pressure in the pulmonary circulation.

Acetylcholine↗