Catestatin attenuates the effects of intrathecal nicotine and isoproterenol.
Catestatin (Cts; human chromogranin A(352-372)) is a neuropeptide derived from chromogranin A (ChgA). In the periphery it is released from the terminals of preganglionic neurons. In the adrenal medulla it inhibits catecholamine release by non-competitively antagonizing nicotinic cholinergic receptors. ChgA is present in the central nervous system, but the extent to which it is present within bulbospinal sympathoexcitatory neurons is unknown. We investigated the distribution of ChgA in the brainstem and its relationship to sympathoexcitatory neurons by combining immunofluorescence and in situ hybridization. A possible role for Cts in modulating the effect of other neurotransmitter systems in the spinal cord was examined by intrathecal injection of Cts, in conjunction with nicotine (1 microg-100 microg) and isoproterenol (0.12 microg-2.5 microg), in the anesthetized rat. Cts attenuated the hypotensive effect of isoproterenol on mean arterial pressure (maximum dose, 2.5 microg isoproterenol; -27 mmHg pre-Cts to -18 mmHg post-Cts), splanchnic sympathetic nerve activity (at 2.5 microg isoproterenol; 10.5% pre-Cts to 2.4% post-Cts), HR (at 2.5 microg isoproterenol; 1.1% pre-Cts to -1.6% post-Cts), and the dp/dt max of carotid pulse pressure (at 2.5 microg isoproterenol 17.3% pre-Cts to 9.3% post-Cts). Cts attenuated the hypertensive effect of nicotine on mean arterial pressure (at 10 microg nicotine, 19.3 mmHg pre-Cts to 6.8 mmHg post-Cts), splanchnic sympathetic nerve activity (at 10 microg nicotine, 10.7% pre-Cts to 4.5% post-Cts), and HR (at 10 microg nicotine, 4.1% pre-Cts to 2.0% post-Cts). The results indicate that Cts antagonizes both central nicotinic acetylcholine receptors and beta-adrenoceptors that are involved in cardiovascular regulation in vivo.
Australian School of Advanced Medicine, Dow-Corning Bldg, Level 1, 3 Innovation Rd, Macquarie University, 2109, NSW, Australia.
Andrea H
AH
Gaede
Mandy S Y
MS
Lung
Paul M
PM
Pilowsky
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000378:metabolism*; D002452:Cell Count; D053379:Chromogranin A / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D007278:Injections, Spinal; D007545:Isoproterenol / Q000008:administration & dosage*; D008297:Male; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009538:Nicotine / Q000008:administration & dosage*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism
D053379:Chromogranin A; D010446:Peptide Fragments; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011978:Receptors, Nicotinic; C109084:chromogranin A (344-364); D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D007545:Isoproterenol