Cyclic GMP mediates neurogenic relaxation in the bovine retractor penis muscle

Abstract

1 Field stimulation of the non-adrenergic, non-cholinergic inhibitory nerves to the bovine isolated retractor penis muscle evoked a relaxation that was preceded by a rise in the tissue content of cyclic GMP. There was no change in the content of cyclic AMP. 2 The selective cyclic GMP phosphodiesterase inhibitor, 2-o-propoxyphenyl-8-azapurin-6-one (M&B 22948), elevated the tissue's cyclic GMP content, and potentiated both the relaxation and the rise in cyclic GMP produced by inhibitory nerve stimulation. 3 Sodium nitroprusside and an inhibitory factor extracted from the bovine retractor penis muscle mimicked the effects of inhibitory nerve stimulation in that they each produced relaxation associated with a selective rise in cyclic GMP concentration. 4 Haemoglobin (in the form of erythrocyte haemolysate) and N-methylhydroxylamine, which are known to block guanylate cyclase, blocked the relaxation and the rise in cyclic GMP content produced by inhibitory nerve stimulation, inhibitory factor and sodium nitroprusside. Haemoglobin itself caused a rise in muscle tone and at the same time reduced the cyclic GMP content of the tissue. 5 8-Bromocyclic GMP, a permeant derivative of cyclic GMP, produced a relaxation of the muscle that, as expected, was not blocked by haemoglobin. 6 Vasoactive intestinal polypeptide, prostaglandin E1 and forskolin each produced relaxation associated with a selective rise in cyclic AMP content. Their effects were not blocked by haemoglobin or N-methylhydroxylamine. 7 It is concluded that inhibitory nerve stimulation in the bovine retractor penis muscle produces a relaxation that is mediated by cyclic GMP, although some substances relax the muscle without affecting cyclic GMP levels. The results are also compatible with the view that the extracts of muscle contain the inhibitory neurotransmitter.

N‐methylhydroxylamine inhibits and M&B 22948 potentiates relaxations of the mouse anococcygeus to non‐adrenergic, non‐cholinergic field stimulation and to nitrovasodilator drugs

“…In the present study, relaxations to nitrovasodilator drugs, like those to NANC stimulation, were blocked by NMH and potentiated by M&B 22948; this suggests that the NANC transmitter of the mouse anococcygeus resembles, in its mode of action, the nitrovasodilators and would be consistent with the possibility that the inhibitory factor, or a closely related substance, is the transmitter released by NANC nerves in the anococcygeus (Bowman & Gillespie, 1982). Whatever the transmitter, it seems clear that NANC transmission in the anococcygeus is the same as that in the retractor penis since NANC relaxations of both tissues are blocked by NMH (Bowman & Drummond, 1984;; this study) and haemolysed blood (Bowman & Gillespie, 1982;Gibson & Tucker, 1982;Gibson & Yu, 1983), are potentiated by M&B 22948 (Bowman & Drummond, 1984;this study), and are insensitive to block by apamin (Bowman & Gillespie, 1982;Gibson & Tucker, 1982).…”

“…Recently, however, Bowman & Drummond (1984 reported that N-methylhydroxylamine (NMH) blocked, and M&B 22948 potentiated, relaxations of the bovine retractor penis to inhibitory factor, NANC field stimulation, and sodium nitroprusside (SNP). These results suggested that the inhibitory factor (or a closely related substance) might be the NANC transmitter of the retractor penis, and that the actions of the transmitter could be mimicked by nitrovasodilator drugs; subsequent studies have revealed that the inhibitory factor may resemble the nitrovasodilators chemically and, like these drugs, may induce smooth muscle relaxation via formation of nitric oxide (NO) with consequent activation of guanylate cyclase (Martin et al, 1988;Gillespie & Sheng, 1988).…”

Hemolysate Inhibits Cerebral Artery Relaxation

“…Therefore, the transmitter substance released from the vasodilator nerve may act on smooth muscle and activate guanylate cyclase, thus increasing cy-N. TODA clic GMP levels, and inhibitions of the relaxant re sponse by hemolysate may result from decreased cyclic GMP production. It is postulated that neuro genic relaxations in the bovine retractor penis muscle is also mediated by cyclic GMP (Bowman and Drummond, 1984).…”

A comparison of haemoglobin and erythrocytes as inhibitors of smooth muscle relaxation by the NANC transmitter in the BRP and rat anococcygeus and by EDRF in the rabbit aortic strip

“…It has, however, several properties in common with EDRF. For example, both relax the BRP (Gillespie & Sheng, 1988a,b), both increase cyclic GMP (Rapoport & Murad, 1983;Diamond & Chu, 1983;Bowman & Drummond, 1984), both are abolished by anoxia (Furchgott & Zawadzki, 1980;Bowman & McGrath, 1985) and by borohydride (Griffith et al, 1984;Gillespie & Sheng, unpublished observation), as well as by haemoglobin. If EDRF is nitric oxide, it is possible that the NANC transmitter is also nitric oxide.…”