Functional Roles of A1-adrenergic Receptors in the Bovine Inferior Alveolar Artery: Regulation of Contraction and Activation of Extracellular Signal Regulated Kinase

The bovine inferior alveoiar artery (BIAA) runs inside the length of the mandibie and branches to form dental arteries that supply blood to the teeth. I investigated the effects of 5-hydroxytryptamine (5-HT), acetylcholine (ACH), calcitonin gene-related peptide (CGRP) and norepinephrine (NE) on vascular tone in the BIAA using functional measurements of contraction. 5-HT potently contracted BIAA rings with an BC50 = 0,81 ± 0.28 pM and was used to pre-contract rings sub-maximally for relaxation experiments. Concentrations of ACH of less than 3 pM caused relaxation of ring segments with an EC50 = 0.10 + 0.02 pM, while concentrations greater than 3 pM caused contraction. CGRP was a full agonist for vasodilation with an EC50 = 0.30 ± .02 pM, and relaxed the arteries via a non-nitric oxide, endothelium-independent mechanism. CGRP8-37 antagonized CGRP induced-vasodilation with low affinity (K.s = 2.71 ± 0.5 pM), suggesting that CGRP causes vasodilation through stimulation of CGRP 2 receptors. NE contracted BIAA rings with low potency (EC50 =11+2.0 pM), which was not due to metabolism of NE or stimulation of 0.2- or [3-adrenergic receptors (ARs). The cp-AR selective antagonist BE 2254 antagonized NE-induced contraction with high affinity, suggesting that NE contracts BIAA rings through stimulation of op-ARs. Affinity values for the op-AR subtype selective antagonists 5-methylurapidil (cpA-AR), WB4101(opA- AR), cyclazosin (cpB-AR) and BMY 7378 (cpo-AR) indicated that NE stimulates contraction through activation of aiA-ARs. This result was supported by the detection of ata-AR mRNA in the BIAA using RT-PCR. Lack of [^Hj-prazosin specific binding in radioligand experiments and low affinity prazosin antagonism of NE-induced contractions suggested that the putative a.]L-AR may be coupled to contraction. The prazosin low affinity was not a result of prazosin removal mechanisms (Transport P), as the Transport P inhibitor desipramine had no effect on prazosin affinity. Taken together, these data demonstrate that numerous vasoactive neurotransmitters contribute to the overall regulation of blood flow to the teeth and oral tissues.

Grantor dc:publisher

Creighton University

Year dc:date.issued

2002

Author dc:creator

• Hague, Chris

Advisor dc:contributor.advisor

• Abel, Peter W.

Statement dc:rights

• Copyright is retained by the Author. A non-exclusive distribution right is granted to Creighton University and to ProQuest following the publishing model selected above.

Language dc:language.iso

en_US

Handle dc:identifier.uri

http://hdl.handle.net/10504/66700

OAI identifier oai:identifier

oai:cdr.creighton.edu:10504/66700