Vol. 289, Issue 1, 354-360, April 1999

Precontraction with Elevated Concentrations of Extracellular Potassium Enables both 5-HT_1B and 5-HT_2A "Silent" Receptors in Rabbit Ear Artery

James R. Smith, Cheol Kim, Heather Kim and Ralph E. Purdy

Department of Pharmacology, College of Medicine, University of California, Irvine, California

The present study was conducted to determine the effect of a small (<10%) K⁺-induced precontraction on the response to vasoconstrictors in the rabbit aorta and ear artery rings. In both tissues, 15 mM K⁺ shifted the methoxamine concentration response curve (CRC) approximately 2.4-fold to the left. There was no change in the sensitivity of the control and amplified CRCs to the ₁ adrenoceptor antagonist prazosin (100 nM). In the aorta, the CRC for serotonin was shifted 4.5-fold to the left in the presence of 15 mM K⁺, and both the control and amplified CRCs were antagonized equally by the 5-HT_2A antagonist ketanserin (10 nM). In contrast, 16 and 20 mM K⁺ caused up to an approximately 60-fold leftward shift of the serotonin CRC in the rabbit ear artery. This effect of 16 mM K⁺ was not altered by mechanical removal of the endothelium or by in vitro denervation using 6-hydroxydopamine. The K⁺-amplified CRC was insensitive to 100 nM prazosin at serotonin concentrations below 3 µM, but was significantly antagonized by 10 nM ketanserin, suggesting that 5-HT_2A receptors are involved in the K⁺-amplified response. The 5-HT_1B-selective antagonist, GR 127935, did not affect control responses to serotonin, but significantly blocked the K⁺-amplified response. Furthermore, the combination of ketanserin and GR 127935 produced a significantly greater blockade of the amplified response than either antagonist alone, supporting the conclusion that both 5-HT_2A and 5-HT_1B receptors mediate the K⁺-amplified response to serotonin in the rabbit ear artery.