VIP and the lung
1
Sl 1 VIP AND THE LUNG Saml I. Said, Oklahoma Hlth. Sc. Cntr and VA Med. Cntr, Oklahoma City, USA. The vasodilator activity attributable to VlP was first discovered in the lung. Though its overall concentration in the lung is considerably lower than in brain or gut,the peptide appears to play an important role in lung physiology and disease. VIP-irm,unoreactivlty in the tracheo-bronchial tree is present in nerve fibres and nerve terminals in the smooth muscle layer,around submucosal glands,in the walls of blood vessels,and in gangllon-like clusters of neuronal cell bodies.VIP immunofluo- rescence has also been reported in murine mast cells in the lung,though its chemi- cal identity has not been confirmed.VIP exerts important biological actions on all pulmonary structures that it innervates.Thus it: l)relaxes tracheo-bronchlal smooth muscle and protects against bronchoconstriction induced by histamine,prostaglandin F2~,or leukotrlene D 4 in dogs and guinea pigs;2)relaxes pulmonary vascular smooth muscle and reduces pulmonary vasoconstriction;3)stimulates water and ion transport in tracheal epithelium,and macromolecular secretion by tracheal submucosal glands of the ferret;and 4)inhibits immunologic release of histamine. Specific VIP recep- tors have been identified in membrane preparations of rat,mouse,guinea pig and hu- man lungs and in human tumor cells.Autoradiographic techniques demonstrate VIP up- take sites in airways and in alveolar walls.Pulmonary VIP receptors have been map- ped immunocytochemically,based on the ability of VIP to stimulate cyclic AMP prod- uction.The physiological role of VIP in the lung is under active investigatlon. Sev- eral lines of evidence point to VIP as a transmitter of the nonadrenergic,nonchol- inergic relaxation of airways.Preliminary data suggest that it may also be a trans- mitter of the same system in pulmonary vessels. VIP may also modulate bronchial gland secretion of ions,water and macromolecules.Potential therapeutic applications for VIP,now being tested,include the treatment and prevention of bronchial asthma, t],~ relief of pulmonary vasoconstriction, and the attenuation of acute lung injury. PROTEIN- AND I~-BINDING CAPACITY OF VIP AND OTHER BASIC NEUROHORMONAL PEPTIDES L.I. Larsson, L. Scowl and B.L. Wan~ Onlt of Histochelalstry, University Institute of Patholgical Anatomy, DK-2100 COPENHAGEN, DANEMARK. Many workers have noted that cer~aln neurohormonsl c~,lIA and nerves display unspecific binding of IgG. Such binding has by some been ascribed to charge effects and has been suggested to be abated by high pH and high molarity of staining solutions. Others have considered that Clq , the first component of coe~lement, is responsible for the binding. Cells displaying suCh unspecific staining belong to the APOD system and include ACTH-~endorphin-containing pituitary corticotrophs and antropylorlc gastrln cells, cells of the supraoptic nucleus and adrenal medulla, pancreatic glucagon cells and scattered peptiderglc neurons. Common to all of these is their content of basically charged peptides (ACTH, endorphins, glucagon, enkephalins, dynorphins ). By paper cy~cochemical models, we show that such pe~cides, as well as poly-L-lysine strongly binds gold- or Peroxidase-labelled IgG from several species as well as gold-labelled BSA, RSA and protein A. Preabsorptlon of gold-labelled BSA with synthetic ACTH [1-24] or poly-L-lyslne abolishes or greatly quenches the staining of also the other basic Peptides. The binding is not significantly altered by high ~ - high molarity buffers or by 2M urea treatment, however. Characteristically, gold- or peroxidase-labelled proteins bind strongly, whereas Sternbergere PAP complex only binds at very high Peptide concentrations. The results suggest I) that the PAP method is superior for avoiding unspecific binding, 2) that conventional absorption controls not always document i~nunological specificity of binding and 3) that great care must be exerted, not only when immunocytochemical, but also when ELISA immunoblotting and immune- affinity ex~eri~nts with basic peptides are interpreted.
Transcript of VIP and the lung
Sl 1
VIP AND THE LUNG Saml I. Said, Oklahoma Hlth. Sc. Cntr and VA Med. Cntr, Oklahoma City, USA.
The vasodilator activity attributable to VlP was first discovered in the lung. Though its overall concentration in the lung is considerably lower than in brain or gut,the peptide appears to play an important role in lung physiology and disease. VIP-irm, unoreactivlty in the tracheo-bronchial tree is present in nerve fibres and nerve terminals in the smooth muscle layer,around submucosal glands,in the walls of blood vessels,and in gangllon-like clusters of neuronal cell bodies.VIP immunofluo- rescence has also been reported in murine mast cells in the lung,though its chemi- cal identity has not been confirmed.VIP exerts important biological actions on all pulmonary structures that it innervates.Thus it: l)relaxes tracheo-bronchlal smooth muscle and protects against bronchoconstriction induced by histamine,prostaglandin F2~,or leukotrlene D 4 in dogs and guinea pigs;2)relaxes pulmonary vascular smooth muscle and reduces pulmonary vasoconstriction;3)stimulates water and ion transport in tracheal epithelium,and macromolecular secretion by tracheal submucosal glands of the ferret;and 4)inhibits immunologic release of histamine. Specific VIP recep-
tors have been identified in membrane preparations of rat,mouse,guinea pig and hu- man lungs and in human tumor cells.Autoradiographic techniques demonstrate VIP up- take sites in airways and in alveolar walls.Pulmonary VIP receptors have been map- ped immunocytochemically,based on the ability of VIP to stimulate cyclic AMP prod- uction.The physiological role of VIP in the lung is under active investigatlon. Sev- eral lines of evidence point to VIP as a transmitter of the nonadrenergic,nonchol- inergic relaxation of airways.Preliminary data suggest that it may also be a trans- mitter of the same system in pulmonary vessels. VIP may also modulate bronchial gland secretion of ions,water and macromolecules.Potential therapeutic applications for VIP,now being tested,include the treatment and prevention of bronchial asthma, t],~ relief of pulmonary vasoconstriction, and the attenuation of acute lung injury.
PROTEIN- AND I~-BINDING CAPACITY OF VIP AND OTHER BASIC NEUROHORMONAL PEPTIDES L.I. Larsson, L. Scowl and B.L. Wan~ Onlt of Histochelalstry, University Institute of Patholgical Anatomy, DK-2100 COPENHAGEN, DANEMARK.
Many workers have noted that cer~aln neurohormonsl c~,lIA and nerves display unspecific binding of IgG. Such binding has by some been ascribed to charge effects and has been suggested to be abated by high pH and high molarity of staining solutions. Others have considered that Clq , the first component of coe~lement, is responsible for the binding. Cells displaying suCh unspecific staining belong to the APOD system and include ACTH-~endorphin-containing pituitary corticotrophs and antropylorlc gastrln cells, cells of the supraoptic nucleus and adrenal medulla, pancreatic glucagon cells and scattered peptiderglc neurons. Common to all of these is their content of basically charged peptides (ACTH, endorphins, glucagon, enkephalins, dynorphins ). By paper cy~cochemical models, we show that such pe~cides, as well as poly-L-lysine strongly binds gold- or Peroxidase-labelled IgG from several species as well as gold-labelled BSA, RSA and protein A. Preabsorptlon of gold-labelled BSA with synthetic ACTH [1-24] or poly-L-lyslne abolishes or greatly quenches the staining of also the other basic Peptides. The binding is not significantly altered by high ~ - high molarity buffers or by 2M urea treatment, however. Characteristically, gold- or peroxidase-labelled proteins bind strongly, whereas Sternbergere PAP complex only binds at very high Peptide concentrations. The results suggest I) that the PAP method is superior for avoiding unspecific binding, 2) that conventional absorption controls not always document i~nunological specificity of binding and 3) that great care must be exerted, not only when immunocytochemical, but also when ELISA immunoblotting and immune- affinity ex~eri~nts with basic peptides are interpreted.
