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Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle.
J Pharmacol Exp Ther. 1999 Jul; 290(1):66-75.JP

Abstract

Pituitary adenylate cyclase-activating peptide (PACAP)1-27, PACAP1-38, and vasoactive intestinal peptide (VIP) initiated dose-dependent contractions of canine ileal circular muscle after intra-arterial injection in vivo or ex vivo. PACAP1-27- and VIP-induced contractions approached the tissue maximum; VIP was 100-fold less potent. PACAP1-38 was more potent than VIP. PACAP1-27 contractions in vivo were unaffected by hexamethonium, reduced equally by atropine or atropine plus hexamethonium, and abolished by tetrodotoxin (TTX), suggesting that PACAP released acetylcholine and another excitatory neurotransmitter from postganglionic cholinergic enteric nerves. In myenteric plexus-free circular muscle strips, PACAP1-27 at 10(-9) M and PACAP1-38 or VIP at 10(-7) M increased [3H]acetylcholine release during nerve stimulation, suggesting the locus of one postganglionic site at which PACAP1-27 acts. All agonists inhibited nerve-mediated contractions in vivo with a potency rank order similar to that for excitation. Inhibition of nitric oxide (NO) synthetase or TTX decreased the duration and amplitude of PACAP1-27- but not PACAP1-38-induced inhibition. Inhibition of NO synthetase abolished VIP-induced inhibition, but TTX did not. Submaximal contractions to acetylcholine were amplified by PACAP1-27 or VIP before TTX and inhibited after TTX. Thus, both PACAP molecules and VIP directly inhibit and indirectly excite smooth muscle contractions. PACAP1-27 and VIP also release NO. The functional potency differences between PACAP1-27 and VIP suggest PAC1 receptors mediate all responses, likely through the stimulation of adenylate cyclase.

Authors+Show Affiliations

Department of Biomedical Science, McMaster University, Hamilton, Ontario, Canada.No affiliation info availableNo 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

10381761

Citation

Fox-Threlkeld, J A., et al. "Pituitary Adenylate Cyclase-activating Peptide as a Neurotransmitter in the Canine Ileal Circular Muscle." The Journal of Pharmacology and Experimental Therapeutics, vol. 290, no. 1, 1999, pp. 66-75.
Fox-Threlkeld JA, McDonald TJ, Woskowska Z, et al. Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle. J Pharmacol Exp Ther. 1999;290(1):66-75.
Fox-Threlkeld, J. A., McDonald, T. J., Woskowska, Z., Iesaki, K., & Daniel, E. E. (1999). Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle. The Journal of Pharmacology and Experimental Therapeutics, 290(1), 66-75.
Fox-Threlkeld JA, et al. Pituitary Adenylate Cyclase-activating Peptide as a Neurotransmitter in the Canine Ileal Circular Muscle. J Pharmacol Exp Ther. 1999;290(1):66-75. PubMed PMID: 10381761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pituitary adenylate cyclase-activating peptide as a neurotransmitter in the canine ileal circular muscle. AU - Fox-Threlkeld,J A, AU - McDonald,T J, AU - Woskowska,Z, AU - Iesaki,K, AU - Daniel,E E, PY - 1999/6/25/pubmed PY - 1999/6/25/medline PY - 1999/6/25/entrez SP - 66 EP - 75 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 290 IS - 1 N2 - Pituitary adenylate cyclase-activating peptide (PACAP)1-27, PACAP1-38, and vasoactive intestinal peptide (VIP) initiated dose-dependent contractions of canine ileal circular muscle after intra-arterial injection in vivo or ex vivo. PACAP1-27- and VIP-induced contractions approached the tissue maximum; VIP was 100-fold less potent. PACAP1-38 was more potent than VIP. PACAP1-27 contractions in vivo were unaffected by hexamethonium, reduced equally by atropine or atropine plus hexamethonium, and abolished by tetrodotoxin (TTX), suggesting that PACAP released acetylcholine and another excitatory neurotransmitter from postganglionic cholinergic enteric nerves. In myenteric plexus-free circular muscle strips, PACAP1-27 at 10(-9) M and PACAP1-38 or VIP at 10(-7) M increased [3H]acetylcholine release during nerve stimulation, suggesting the locus of one postganglionic site at which PACAP1-27 acts. All agonists inhibited nerve-mediated contractions in vivo with a potency rank order similar to that for excitation. Inhibition of nitric oxide (NO) synthetase or TTX decreased the duration and amplitude of PACAP1-27- but not PACAP1-38-induced inhibition. Inhibition of NO synthetase abolished VIP-induced inhibition, but TTX did not. Submaximal contractions to acetylcholine were amplified by PACAP1-27 or VIP before TTX and inhibited after TTX. Thus, both PACAP molecules and VIP directly inhibit and indirectly excite smooth muscle contractions. PACAP1-27 and VIP also release NO. The functional potency differences between PACAP1-27 and VIP suggest PAC1 receptors mediate all responses, likely through the stimulation of adenylate cyclase. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/10381761/Pituitary_adenylate_cyclase_activating_peptide_as_a_neurotransmitter_in_the_canine_ileal_circular_muscle_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=10381761 DB - PRIME DP - Unbound Medicine ER -