Effect of prodynorphin-derived opioid peptides on the ovulatory luteinizing hormone surge in the proestrous rat.
The objective of this study was to determine whether prodynorphin-derived opioid peptides could block the spontaneous luteinizing hormone (LH) surge and ovulation, and if so, whether this inhibitory action was mediated through kappa-opioid receptors. Various doses of dynorphin peptides (dynorphin A(1-17), dynorphin A(1-8), dynorphin B, alpha- and beta-neoendorphin) were infused into the brain through third-ventricle cannulae in rats between 1330-1800 h on proestrus. Each dynorphin peptide blocked the LH surge and ovulation in a dose-dependent manner. Dynorphin A(1-17) and A(1-8) were equally effective in producing these actions, and more potent than either dynorphin B or alpha- or beta-neoendorphin. U50,488H, a specific kappa-opioid receptor agonist, also blocked the LH surge and ovulation. When a mixture of five dynorphin peptides was infused intraventricularly, each at a dose that inhibited the LH surge, both the surge and ovulation were blocked. However, when norbinaltorphimine, a specific kappa-opioid receptor antagonist, was coinfused with the mixture of dynorphin peptides, the LH surge and ovulation were fully restored. These results demonstrate that prodynorphin-derived opioid peptides, acting through kappa-opioid receptors, can block the LH surge and ovulation. Dynorphin A(1-17) and A(1-8) are the most potent in this regard.
Zhang
Qiang
Q
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269-4156, USA.
Gallo
Robert V
RV
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects; D004399:Dynorphins / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D007986:Luteinizing Hormone / Q000378:metabolism*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010060:Ovulation / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology; D011359:Proestrus; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000037:antagonists & inhibitors
D004745:Enkephalins; D010446:Peptide Fragments; D011498:Protein Precursors; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D004399:Dynorphins; C026770:dynorphin (1-8); D007986:Luteinizing Hormone; C033660:preproenkephalin