Intracellular fragments of the natriuretic peptide receptor-C (NPR-C) attenuate dopamine efflux.

Abstract

Natriuretic peptides suppress adrenergic neurotransmission by a mechanism apparently involving the natriuretic peptide receptor-C (NPR-C) rather than particulate guanylyl cyclase receptors. The bulk of evidence implicating the NPR-C in neuromodulatory effects relies on the pharmacological specificity of peptides believed to be specific for the NPR-C. This study tests for NPR-C effects on neurotransmitter release by examining fragments of the receptor for biological activity in pheochromocytoma (PC12) cells permeabilized with digitonin. A pentadecapeptide segment of the cytoplasmic portion of the NPR-C mimicked the effect of natriuretic peptides to suppress dopamine efflux evoked by calcium approximately 40%. Furthermore, an antibody generated against the pentadecapeptide fragment abolished the neuromodulatory effect of C-type natriuretic peptide in permeabilized cells. In contrast, the carboxy terminal nonadecapeptide portion of the NPR-C failed to attenuate dopamine efflux. These data are consistent with the proposed role of the NPR-C in transducing the biological activity of natriuretic peptides in adrenergic tissue. The most novel aspect of these observations involves the potency of the small cytosolic region of the NPR-C with the region closest to the membrane accounting for neuromodulatory effects.

• Authors: S Kanwal, D G Lowe, G J Trachte
• Journal: Endocrinology (Endocrinology) Vol. 140 Issue 3 Pg. 1118-24 (Mar 1999) ISSN: 0013-7227 [Print] United States
• PMID: 10067834 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Neurotransmitter Agents
• Peptide Fragments
• Adenylyl Cyclases
• Guanylate Cyclase
• Receptors, Atrial Natriuretic Factor
• atrial natriuretic factor receptor C
• Digitonin
• Dopamine

Topics

• Adenylyl Cyclases (metabolism)
• Amino Acid Sequence
• Analysis of Variance
• Animals
• Antibody Formation
• Cell Membrane Permeability (drug effects)
• Cytosol (chemistry)
• Digitonin (pharmacology)
• Dopamine (metabolism)
• Guanylate Cyclase (chemistry)
• Molecular Sequence Data
• Neurotransmitter Agents (metabolism, physiology)
• PC12 Cells
• Peptide Fragments (immunology, physiology)
• Rats
• Receptors, Atrial Natriuretic Factor (chemistry)