The effects of K+ channel blockers on ovine parotid secretion depend on the mode of stimulation.
The vascularly isolated parotid glands of sheep were submaximally stimulated for 4 min by nerve stimulation, or by infusion of acetylcholine (ACh) or bethanechol directly into the artery supplying the gland. The three modes of stimulation caused almost equal increases in the rate of salivary flow, initial losses of K+ and phosphate from the gland and total glandular deficits of K+ and phosphate. Concurrent arterial infusion of the K+ channel blocker tetraethylammonium (TEA), at 1.5-3.3 mM in blood, almost abolished these responses to bethanechol but did not alter the responses to nerve stimulation or ACh. The responses to bethanechol were restored by increasing the concentration fourfold. Concurrent arterial infusion of 4-aminopyridine (4-AP), at 0.1-2.3 mM in blood, partially inhibited the increase in salivary flow due to bethanechol but not the response to nerve stimulation or ACh. The specificity and competitive nature of the action of TEA and 4-AP on responses to direct muscarinic stimulation by bethanechol are consistent with blockade of K+ channels in secretory end-piece cells. The failure of TEA and 4-AP to inhibit responses to nerve stimulation and ACh may be due to the blocking agents potentiating the release of neurotransmitter ACh. It is also possible that nerve stimulation and ACh may cause the release of a co-transmitter which bethanechol does not.
Wright
R D
RD
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
Blair-West
J R
JR
D015761:4-Aminopyridine / Q000494:pharmacology*; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D004558:Electric Stimulation; D010306:Parotid Gland / Q000187:drug effects / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D012463:Saliva / Q000378:metabolism; D012756:Sheep; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D001626:Bethanechol Compounds; D010710:Phosphates; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D018723:Bethanechol; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D000109:Acetylcholine; D011188:Potassium