TY - JOUR T1 - PHARMACOLOGY OF THE CROP (ESOPHAGEAL) MUSCLES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 387 LP - 441 VL - 33 IS - 4 AU - P. J. HANZLIK AU - E. M. BUTT Y1 - 1928/08/01 UR - http://jpet.aspetjournals.org/content/33/4/387.abstract N2 - In this section, the outstanding features and peculiarities of the active drugs on the crop muscles are briefly summarized. The [See table in the PDF file] discussion of the details of the actions and of comparisons with actions on other portions of the alimentary tract and in other species2 have been given in the text with each drug. Table 1 summarizes the effective drugs according to their action on the circular and longitudinal muscles together and indicates the probable seat of action of each drug. An outstanding feature with a number of the drugs was the reciprocal response, i.e., contraction of the circular with simultaneous relaxation of the longitudinal muscle. It is seen that the reciprocation occurred only with stimulants, or during the stimulant phase of a drug's action. However, there was no uniformity among the drugs as to the seat of action, at least according to the analyses made by us. The majority of those used acted directly upon muscle, namely, apocodeine, barium, histamine, morphine (occasionally), peptone and tyramine. However, reciprocation was also caused by the parasympathomimetic agents, choline and physostigmine (in small doses), and also by epinephrine, which acted on the sympathetic nerves or myoneural junctions, and by nicotine during initial ganglionic stimulation. It will be recalled from a previous paper that reciprocation of the crop muscles occurs also during spontaneous peristalsis; in response to electrical vagus stimulation and to the distention pressure stimulus (2), and in anaphylactic shock (3). The one common factor in these mechanical reciprocations is a contracting or stimulated circular muscle, and the same is true of the drug reciprocations. Drugs which do not cause contraction, but on the contrary cause a relaxation of the circular muscle, namely, papaverine, chelidonine, and atropine, do not cause a reciprocal response (contraction) of the longitudinal muscle of the untreated crop under tension. Exceptions must be noted in cases where the tonus state of the longitudinal muscle has been altered by previous treatment. The exceptional case of circular muscle contraction not resulting in reciprocal relaxation of the longitudinal muscle is electrical sympathetic nerve stimulation described previously (2). In agreement with this is the epinephrine stimulation of both muscles of the untreated crop, although here too an altered functional state may give a different result. During sympathetic nerve stimulation, the circular muscle contracts much less than it does during vagus stimulation, so it would seem that a rather marked excitation of this muscle is necessary for the reciprocation. It is tempting to suggest that the drug reciprocations here described are mediated through the myenteric reflex as in the case of distention pressures and of vagus stimulation, but drug stimuli do not necessarily evoke responses in the same way as mechanical or electrical stimuli. There may be a direct action on the myenteric plexuses alone, or a direct action in conjunction with a reflex from the contracting muscle. Certain difficulties in this suggestion arise from the fact that not all agents causing circular muscle contraction through direct muscle stimulation evoke a reciprocal response of the longitudinal muscle, notably after acetic acid (change in pH), cocaine, ephedrine, ergotoxine, guanidine, morphine, peptone (in large doses), phenylethanolamine, physostigmine (in large doses) and pilocarpine. These drugs caused the same response (stimulation) in both muscles, but all of them, with the exception of guanidine and physostigmine, were relatively weak stimulants of circular muscle. This would still leave a strong circular contraction as indispensable to reciprocation. More difficulties, however, arise from the fact that the parasympathetic stimulants, arecoline, choline and pilocarpine, which gave marked contractions of the circular muscle, did not cause reciprocation. Probably dosage of the drug influences the outcome. Our evidence is inadequate to cover all the possibilities that may be involved; hence the question of the mechanism of the reciprocal response after drugs must be left open. The results of the paper emphasize that traditional muscular and autonomic nerve stimulants do not necessarily stimulate, nor do they necessarily stimulate or contract both muscle coats in the same organ when they stimulate or contract one of them. Considerable has been said regarding the altered functional state in determining the variability of the response of certain drugs, but this and various examples will be summarized separately. The results as a whole indicate the value of comparative pharmacology for a better and more comprehensive understanding of drug actions. The method used commends itself for simplicity, directness of approach, and freedom from difficulties which often defeat or complicate experimentation with other portions of the alimentary tract in situ. ER -