Calcitonin gene-related peptide in noradrenergic transmission in rat hypothalamus.
In the present study, we examined the regulatory mechanisms of calcitonin gene-related peptide on norepinephrine release in rat hypothalamus. Calcitonin gene-related peptide inhibited the stimulation-evoked norepinephrine release from hypothalamic slices of Sprague-Dawley rats in a dose-dependent manner, although the peptide did not affect basal release of norepinephrine. The blockade of the alpha 2-adrenergic receptors by RX 781094 failed to modulate the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. Pretreatment of slices with islet activating protein, a toxin that interferes with the coupling of the inhibitory receptors to adenylate cyclase, did not affect the suppression of norepinephrine release by calcitonin gene-related peptide. However, Bay K 8644, a dihydropyridine-sensitive calcium channel agonist, significantly reversed the inhibitory effects of calcitonin gene-related peptide on norepinephrine release. These results show that calcitonin gene-related peptide might inhibit norepinephrine release in rat hypothalamus, partially mediated by interactions with dihydropyridine-sensitive Ca2+ channels but not by interactions with presynaptic alpha 2-adrenergic receptors and inhibitory guanosine triphosphate binding proteins. Furthermore, the finding suggests the possible involvement of calcitonin gene-related peptide in the regulation of sympathetic nervous activity in the central nervous system.
Tsuda
K
K
Division of Cardiology, Wakayama Medical College, Japan.
Tsuda
S
S
Goldstein
M
M
Nishio
I
I
Masuyama
Y
Y
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D004146:Dioxanes / Q000494:pharmacology; D004338:Drug Combinations; D004558:Electric Stimulation; D007031:Hypothalamus / Q000502:physiology*; D019329:Idazoxan; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D004338:Drug Combinations; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015740:Calcitonin Gene-Related Peptide; D019329:Idazoxan