The Response of the Costo‐uterine Muscle of the Rat to Adrenoreceptor Agonists During the Oestrous Cycle: A Comparison With the Uterine Horn

Abstract

Adrenoreceptors in the rat costo‐uterine muscle were compared with those in the uterine horn. The responses of electrically‐stimulated preparations of both tissues to isoprenaline and phenylephrine were investigated in the absence and presence of phentolamine and propranolol to block α‐ and β‐adrenoreceptors respectively. Preparations were taken from rats at known stages of the four‐day oestrous cycle. Both adrenoreceptor agonists consistently inhibited contractions in both tissues; threshold sensitivity to isoprenaline was similar for both tissues and at all cycle stages. The same held true for phenylephrine, which was only approximately 1/400 as potent as isoprenaline. A generally similar pattern was observed when concentrations producing maximum inhibition were compared; however during proestrus, phenylephrine was more potent in producing maximal responses in uterine horns than in costo‐uterine muscles. Phentolamine had no effect on inhibitory responses to isoprenaline in either tissue, nor to phenylephrine in costo‐uterine muscles, but slightly enhanced the inhibitory action of phenylephrine in uterine horns from proestrous rats. Propranolol blocked the inhibitory effects of both drugs, revealing an excitatory effect of phenylephrine in the uterine horns at proestrus. These observations, and estimates of pA2 values for propranolol against both agonists, indicate that β‐adrenoreceptors insensitive to cyclical fluctuations in ovarian hormone levels, are predominant in the uterine horn and may be the exclusive adrenoreceptor present in the costo‐uterine muscle. In the uterine horn a small sub‐population of excitatory α‐adrenoreceptors, the presence of which is masked by β‐adrenoreceptors, can be demonstrated during proestrus. These receptors may be dependent upon the presence of the endometrium and/or the circular smooth muscle layer. The costo‐uterine muscle, which lacks excitatory α‐adrenoreceptors, could serve as a useful model of the longitudinal layer of the myometrium in investigations of drug actions at β‐adrenoreceptors.

The costo‐uterine muscle of the rat contains a homogeneous population of β‐adrenoceptors

“…As we have shown previously (Hartley & Pennefather, 1981;1984a), preparations responded regularly to electrical field stimulation for periods of 5-6 h. All amines used produced only inhibition of electricallyevoked contractions. Figure 1 shows the inhibitory effects of fenoterol and adrenaline upon evoked-contractions of costo-uterine muscle preparations.…”

“…Both phenylephrine and isoprenaline reduced the size of contractions. These effects were unaffected by phentolamine but were antagonized though not reversed by propranolol (Hartley & Pennefather, 1981). We, therefore, suggested that the adrenoceptors within the tissue are exclusively of the ,-type.…”

“…Vaginal smears were taken from each rat before experimentation and cycle stage determined histologically; we have previously shown that cycle stage does not influence the inhibitory potencies of either isoprenaline or phenylephrine on this preparation (Hartley & Pennefather, 1981).…”

“…The methods for setting up isolated preparations of costo-uterine muscle, for electrical stimulation and for recording of contractions, have been described by us previously (Hartley & Pennefather, 1981;1984a). In brief, the tissues were attached to holders incorporating platinum electrodes.…”

(±)‐pindolol Has Β2‐adrenoceptor Antagonist but Not Agonist Action on the Costo‐uterine Muscle of the Rat

“…The rat costo-uterine muscle connects the tuba1 end of the uterine horn to the lower ribs (Gabella 1976). Studies with field-stimulated (Hartley & Pennefather 1981 and carbacholcontracted (Henry et al 1984(Henry et al , 1985 preparations have established that this smooth muscle contains adrenoceptors solely of the &subtype which mediate physiological antagonism of contrac-tile stimuli. These P,-receptors are efficiently coupled to the processes mediating inhibitory effects, since the &adrenoceptor selective agonists noradrenaline and R0363 [( +)-1-(3,Cdimethoxyphenethylamino)-3-(3,4-dihydroxyphenoxy)-2-propanol oxalate] (Raper et al 1978;Iakovidis et al 1980), produce full inhibition of electrically evoked contractions, and are blocked selectively by the P2-adrenoceptor antagonist, ICI 118,551 .…”