Journal article
Tachyphylaxis to PACAP-27 after inhibition of NO synthesis: a loss of adenylate cyclase activation
American journal of physiology. Regulatory, integrative and comparative physiology, Vol.277(5), pp.R1453-R1461
11/01/1999
DOI: 10.1152/ajpregu.1999.277.5.R1453
PMID: 10564219
Abstract
The vasodilator effects of pituitary adenylate cyclase activating polypeptide (PACAP-27) are subject to tachyphylaxis in rats treated with the nitric oxide synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME). This study examined whether this tachyphylaxis is due to the loss of vasodilator potency of cAMP generated by activation of the Gs protein-coupled PACAP receptors. Five successive treatments with PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats that were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in l-NAME (50 μmol/kg iv)-treated rats produced vasodilator responses of similar magnitude to those in saline-treated rats, whereas four subsequent injections produced progressively and markedly smaller responses. The hemodynamic effects of the membrane-permeable cAMP analog 8-(4-chlorophenylthiol)-cAMP (8-CPT-cAMP; 5–15 μmol/kg iv) were similar inl-NAME-treated rats and inl-NAME-treated rats that had received the five injections of PACAP-27. In addition, five injections of 8-CPT-cAMP (10 μmol/kg iv) produced pronounced vasodilator responses in saline- andl-NAME-treated rats that were not subject to the development of tachyphylaxis. These results suggest that a loss of biological potency of cAMP is not responsible for tachyphylaxis to PACAP-27 inl-NAME-treated rats. This tachyphylaxis may be due to the inability of the Gs protein-coupled PACAP receptor to activate adenylate cyclase.
Details
- Title: Subtitle
- Tachyphylaxis to PACAP-27 after inhibition of NO synthesis: a loss of adenylate cyclase activation
- Creators
- Erin J Whalen - Departments of Pharmacology and Psychology and The Cardiovascular Center, The University of Iowa, Iowa City, Iowa 52242Alan Kim Johnson - Departments of Pharmacology and Psychology and The Cardiovascular Center, The University of Iowa, Iowa City, Iowa 52242Stephen J Lewis - Departments of Pharmacology and Psychology and The Cardiovascular Center, The University of Iowa, Iowa City, Iowa 52242
- Resource Type
- Journal article
- Publication Details
- American journal of physiology. Regulatory, integrative and comparative physiology, Vol.277(5), pp.R1453-R1461
- DOI
- 10.1152/ajpregu.1999.277.5.R1453
- PMID
- 10564219
- NLM abbreviation
- Am J Physiol Regul Integr Comp Physiol
- ISSN
- 0363-6119
- eISSN
- 1522-1490
- Language
- English
- Date published
- 11/01/1999
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
- Record Identifier
- 9984213430002771
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