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Pharmacological characterization of presynaptic calcitonin gene-related peptide (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric resistance vessels.
J Pharmacol Exp Ther. 1994 Jan; 268(1):59-64.JP

Abstract

Rat mesenteric arteries are innervated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRP nerves). This study investigated the presence of presynaptic CGRP receptors on CGRP nerves and the receptors' role in the regulation of CGRP release from these nerves. The rat mesenteric vascular bed was perfused with Krebs' solution containing 7 microM methoxamine plus 5 microM guanethidine to produce active tone and block adrenergic neurotransmission. In this preparation, periarterial nerve stimulation (PNS;2 Hz) and bolus infusion of CGRP (50 pmol) caused a decrease in perfusion pressure caused by vasodilation. Vasodilator response to PNS was abolished by 0.3 microM tetrodotoxin and by 1 microM human CGRP[8-37] (CGRP[8-37]), a CGRP receptor antagonist, which also abolished the response to bolus infusion of CGRP. Perfusion of CGRP (0.03-0.5 nM) dose-dependently inhibited vasodilator response to PNS, whereas it did not affect the response to bolus infusion of CGRP. The inhibitory effect of CGRP (0.3 nM) was antagonized by CGRP[8-37] (3 and 10 nM). Lower concentrations of CGRP[8-37] (1-10 nM) potentiated the vasodilator response to PNS, but higher concentrations (100 nM-1 microM) inhibited the response. The vasodilator response to bolus infusion of CGRP was dose-dependently inhibited by CGRP[8-37]. Eel calcitonin (5 and 50 microM), forskolin (0.01 and 0.1 microM), 3-isobutyl-1-methylxanthine (0.3 and 1 microM) and cyclic 8-bromo-adenosine 3':5'-monophosphate (10 and 100 microM) had no effect on the PNS-induced vasodilation. These results suggest that CGRP nerves are endowed with presynaptic CGRP receptors, which regulate CGRP release from the nerves via a negative feedback mechanism.

Authors+Show Affiliations

Department of Pharmacology, Miyazaki Medical College, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7507998

Citation

Nuki, C, et al. "Pharmacological Characterization of Presynaptic Calcitonin Gene-related Peptide (CGRP) Receptors On CGRP-containing Vasodilator Nerves in Rat Mesenteric Resistance Vessels." The Journal of Pharmacology and Experimental Therapeutics, vol. 268, no. 1, 1994, pp. 59-64.
Nuki C, Kawasaki H, Takasaki K, et al. Pharmacological characterization of presynaptic calcitonin gene-related peptide (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric resistance vessels. J Pharmacol Exp Ther. 1994;268(1):59-64.
Nuki, C., Kawasaki, H., Takasaki, K., & Wada, A. (1994). Pharmacological characterization of presynaptic calcitonin gene-related peptide (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric resistance vessels. The Journal of Pharmacology and Experimental Therapeutics, 268(1), 59-64.
Nuki C, et al. Pharmacological Characterization of Presynaptic Calcitonin Gene-related Peptide (CGRP) Receptors On CGRP-containing Vasodilator Nerves in Rat Mesenteric Resistance Vessels. J Pharmacol Exp Ther. 1994;268(1):59-64. PubMed PMID: 7507998.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological characterization of presynaptic calcitonin gene-related peptide (CGRP) receptors on CGRP-containing vasodilator nerves in rat mesenteric resistance vessels. AU - Nuki,C, AU - Kawasaki,H, AU - Takasaki,K, AU - Wada,A, PY - 1994/1/1/pubmed PY - 1994/1/1/medline PY - 1994/1/1/entrez SP - 59 EP - 64 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 268 IS - 1 N2 - Rat mesenteric arteries are innervated by calcitonin gene-related peptide (CGRP)-containing vasodilator nerves (CGRP nerves). This study investigated the presence of presynaptic CGRP receptors on CGRP nerves and the receptors' role in the regulation of CGRP release from these nerves. The rat mesenteric vascular bed was perfused with Krebs' solution containing 7 microM methoxamine plus 5 microM guanethidine to produce active tone and block adrenergic neurotransmission. In this preparation, periarterial nerve stimulation (PNS;2 Hz) and bolus infusion of CGRP (50 pmol) caused a decrease in perfusion pressure caused by vasodilation. Vasodilator response to PNS was abolished by 0.3 microM tetrodotoxin and by 1 microM human CGRP[8-37] (CGRP[8-37]), a CGRP receptor antagonist, which also abolished the response to bolus infusion of CGRP. Perfusion of CGRP (0.03-0.5 nM) dose-dependently inhibited vasodilator response to PNS, whereas it did not affect the response to bolus infusion of CGRP. The inhibitory effect of CGRP (0.3 nM) was antagonized by CGRP[8-37] (3 and 10 nM). Lower concentrations of CGRP[8-37] (1-10 nM) potentiated the vasodilator response to PNS, but higher concentrations (100 nM-1 microM) inhibited the response. The vasodilator response to bolus infusion of CGRP was dose-dependently inhibited by CGRP[8-37]. Eel calcitonin (5 and 50 microM), forskolin (0.01 and 0.1 microM), 3-isobutyl-1-methylxanthine (0.3 and 1 microM) and cyclic 8-bromo-adenosine 3':5'-monophosphate (10 and 100 microM) had no effect on the PNS-induced vasodilation. These results suggest that CGRP nerves are endowed with presynaptic CGRP receptors, which regulate CGRP release from the nerves via a negative feedback mechanism. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/7507998/Pharmacological_characterization_of_presynaptic_calcitonin_gene_related_peptide__CGRP__receptors_on_CGRP_containing_vasodilator_nerves_in_rat_mesenteric_resistance_vessels_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7507998 DB - PRIME DP - Unbound Medicine ER -