Contractile Responses to Phenylephrine and Carbachol in Circular Rabbit Fundus Strips at Varying External K+and Ca++Concentrations

Abstract:Both phenylephrine and carbachol produced dose‐dependent contraction in isolated circular strips from the fundus of rabbit stomachs. The threshold concentration required to produce contraction (phenylephrine 10‐6M, carbachol 2 × 10−7M) remained the same when the external K+concentration ([K+]o) was altered from zero to 94.4 mM, and the external Ca++concentration ([Ca++]o) from zero to 3.75 mM. The magnitude of the contractions produced by the two drugs was greatly altered, however, and these alterations were best seen in the responses to the highest concentrations used (phenylephrine 10−4M, carbachol 2 × 10−5M). The responses to carbachol 2 × 10−5M were significantly (P < 0.05) greater than the response to phenylephrine 10−4M at all [K+]oand [Ca++]oother than [Ca++]o= 0. In order to compare the influence of varying [K+loand [Ca++]oon the responses to the two drugs, the per cent alterations in the responses were studied. The contractions produced by both phenylephrine and carbachol increased when [K+]owas raised from zero to 23.8 mM (P < 0.005), but were reduced when [K+]owas raised further (to 47.2 and 94.4 mM) (P < 0.05). Increasing [Ca++Iogave increasing responses to both drugs. The reduction in the response to phenylephrine 10−4M when [K+]owas reduced from 5.9 mM to zero was less marked than the reduction in the response to carbachol 2 × 10−5M (0.1 > P > 0.05 for the difference), but the increase in the response to phenylephrine when [Ca++]owas increased from 0.31 to 3.75 mM was significantly greater (P < 0.05) than the increase in the response to carbachol. It is suggested that the increase in response with increasing [K+]ofrom zero to 23.8 mM may be due to a secondary increase in available Ca++, while the reduction in response at higher [K+]omay be due to the depolarization which these [K+]oproduce.